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Biomarkers and Immune Resistance in ACC

Immunotherapy

Biomarkers and immune resistance in adrenocortical carcinoma (ACC) describe tumor, microenvironmental, and endocrine features that may influence responsiveness to immunotherapy, especially immune checkpoint blockade. In ACC, this topic lies within the broader domains of immunotherapy, molecular pathology, and endocrine tumor biology. Although checkpoint inhibitors can produce durable remissions in a minority of patients with advanced disease, most ACCs appear substantially less responsive than more immunogenic solid tumors.12

ACC is commonly characterized as an immunologically “cold” malignancy, with low cytolytic activity, limited effector immune infiltration, and transcriptional programs consistent with immune exclusion.345 A distinctive feature of ACC is that immune resistance may be driven not only by tumor-intrinsic biology but also by hormone excess, particularly cortisol hypersecretion, which may suppress antitumor immunity systemically and within the tumor microenvironment.678

Among currently discussed biomarkers, mismatch repair deficiency and microsatellite instability-high status (dMMR/MSI-H) represent the most clinically actionable subgroup, but these abnormalities are uncommon and do not reliably predict benefit in every case.91011 More broadly, the evidence base remains limited: most ACC biomarker data derive from retrospective cohorts, translational analyses, reviews, and case reports rather than large prospective ACC-specific trials.12132 As a result, many candidate biomarkers are better understood as biologic or prognostic signals than as validated tools for routine treatment selection.

Biologic and diagnostic context

ACC differs from many other cancers because immune resistance may reflect the combined effects of oncogenic signaling, low baseline immunogenicity, and endocrine-mediated immunosuppression. Pan-cancer and ACC-focused transcriptomic analyses consistently place ACC among tumors with low cytolytic immune activity, while showing that relatively inflamed tumors tend to have better survival.34 This association is reasonably consistent as a prognostic observation, but it is less reliable as a direct predictor of checkpoint inhibitor response.

The endocrine context is especially important in cortisol-secreting ACC. Across several profiling studies, glucocorticoid excess has been associated with reduced T-cell and NK-cell infiltration, broad suppression of immune-related gene expression, and inferior outcomes.678 This relationship is biologically plausible and supported by convergent retrospective and translational data, though prospective interventional validation is limited. Clinically, biomarker interpretation in ACC may be misleading if hormone secretion status is not assessed alongside molecular and microenvironmental features.1415

Indirect evidence from outside ACC also supports the broader principle that systemic glucocorticoid exposure can impair cancer immunosurveillance, although such evidence does not establish ACC-specific predictive effects.16 Taken together, these findings help explain why standard immuno-oncology biomarkers often perform inconsistently in ACC.

Major biomarker domains

dMMR and MSI-H status

dMMR/MSI-H is the most reproducible biomarker-defined setting in which checkpoint inhibitor benefit has been observed in ACC. Case-based and review-level evidence describes meaningful, sometimes durable responses to PD-1 blockade or combined PD-1/CTLA-4 inhibition, including in Lynch syndrome-associated tumors.17910 This makes MMR immunohistochemistry and MSI assessment clinically relevant in advanced ACC, both for treatment consideration and hereditary cancer evaluation.

However, dMMR and MSI-H are not fully interchangeable in ACC, and dMMR alone does not consistently identify an inflamed tumor phenotype, favorable prognosis, or reliable checkpoint sensitivity.11 The practical implication is that this is the strongest available biomarker domain, but it remains an imperfect predictor and should be interpreted with clinical context, including hormone excess and disease tempo.1811

Cortisol excess and steroid phenotype

Cortisol excess is the most consistent candidate biomarker of immune resistance in ACC. Cortisol-secreting tumors tend to show reduced immune infiltration, less favorable immune transcriptional profiles, and worse clinical outcomes, suggesting that steroid phenotype may shape immunotherapy resistance independently of tumor mutational features.678

This signal appears biologically robust, but it is not yet a validated stand-alone criterion for treatment selection. In practice, the findings support attention to endocrine control when immunotherapy is considered and provide a rationale for investigating combinations with steroidogenesis inhibition or glucocorticoid receptor blockade.715 Reports of response after cortisol reduction are hypothesis-generating, but they remain vulnerable to publication and selection bias.1920

Measures of immune infiltration, including tumor-infiltrating lymphocytes and transcriptomic immune signatures, appear to have prognostic value in ACC. More inflamed tumors generally show better survival, supporting the view that immune exclusion is one feature of aggressive disease biology.364 This is one of the more reproducible observations in the literature, but its clinical utility currently lies more in biologic stratification than in selecting checkpoint therapy.

By contrast, conventional checkpoint biomarkers such as PD-L1 expression have shown inconsistent associations with response, and no assay or threshold has been validated for routine ACC management.1325 Other proposed markers, including CMTM6, Siglec-9, glucocorticoid receptor–related signatures, CD276, and serum or tumor GDF-15, may describe prognosis or immune state, but they remain investigational.212223124

Interpretation of infiltration-based markers also requires caution. Immune-cell abundance does not necessarily indicate effective antitumor immunity, particularly when myeloid or dysfunctional lymphoid programs predominate, and indirect evidence from other tumors reinforces this limitation.252627 Clinically, these markers may be useful for research stratification, but they are not reliable as simple surrogates of immunotherapy sensitivity.

Tumor mutational burden and broader DNA repair features

Tumor mutational burden (TMB) has not shown clear predictive value in ACC overall. Most ACCs appear to have relatively low TMB, and higher TMB has not consistently correlated with immune infiltration, checkpoint expression, or inferred sensitivity to immune checkpoint blockade.28 Compared with some other malignancies, TMB therefore appears to have limited routine usefulness in ACC.

Rare exceptions may occur in tumors with broader DNA repair abnormalities. Exceptional responder reports involving MSI-H disease or unusual repair-related genomic profiles suggest that comprehensive molecular testing may occasionally identify an immunotherapy-sensitive subset.29 These observations are clinically relevant as exceptions, but they are not sufficiently generalizable to support routine reliance on TMB or rare genomic alterations alone.

Evidence for resistance patterns and treatment implications

Across retrospective series, reviews, and reported clinical experiences, checkpoint inhibitors have modest activity in unselected advanced ACC, with objective responses confined to a minority of patients and disease stabilization in some others.122 Relative to surgery for localized disease and established systemic therapy pathways for advanced disease, immunotherapy currently has a more selective and less predictable role.92

The most plausible settings for benefit appear to be biomarker-enriched or biologically favorable subgroups, particularly dMMR/MSI-H tumors and possibly tumors with lower effective glucocorticoid exposure or more inflamed microenvironments.19179 Proposed resistance mechanisms include glucocorticoid-mediated immunosuppression, immune-cell depletion, and oncogenic programs such as Wnt/beta-catenin signaling.15 These mechanisms are recurrent in the literature, but most remain inferential rather than prospectively validated.

This pattern has shifted interest away from checkpoint monotherapy as a broadly effective strategy and toward biomarker-enriched selection, endocrine-aware treatment planning, and combination approaches designed to reduce immune suppression rather than simply intensify checkpoint blockade.30715

Limitations and research directions

Interpretation of the ACC biomarker literature is constrained by small sample sizes, heterogeneous assays, variable outcome definitions, and heavy reliance on retrospective analyses and exceptional case reports.12132 Accordingly, many reported associations may reflect confounding by prior therapy, hormone control, disease burden, or publication bias rather than true predictive value.

Extrapolation from pan-cancer analyses, non-ACC experimental systems, or indirect immune-state studies is especially uncertain. Such work may clarify general principles of tumor immunobiology, but it does not establish ACC-specific clinical utility without direct validation.313233 Similarly, microbiome-based ACC immune claims require caution where source data have been formally questioned.34

At present, the most defensible routine biomarker role is testing for MMR deficiency and MSI, both to identify a potentially responsive subgroup and to detect hereditary cancer syndromes such as Lynch syndrome.91011 Beyond this, most biomarker-guided immunotherapy use in ACC remains investigational. Current research increasingly emphasizes integrated models that combine tumor genomics, immune profiling, and steroid biology, as well as combination strategies intended to counter glucocorticoid-mediated immune resistance.7155

Included Articles

  • PMID 16886963: This case report evaluated autologous dendritic cell vaccination in two patients with metastatic, hypersecretory ACC using tumor lysate loading and a dendritic cell-tumor fusion platform. Vaccination induced antigen-specific cellular immune responses, but no measurable tumor growth control was observed.35
  • PMID 29515971: A pan-cancer transcriptomic analysis found adrenocortical carcinoma among the tumor types with the lowest cytolytic activity, based on GZMA and PRF1 expression. Within the TCGA ACC cohort, however, higher cytolytic activity was associated with improved overall survival, suggesting prognostic relevance of the immune microenvironment.3
  • PMID 30262398: This case report describes mismatch repair-deficient, cortisol-secreting metastatic ACC with rapid progression on pembrolizumab despite a biomarker profile that might suggest immune checkpoint sensitivity. The authors highlight hypercortisolism as a possible cause of immune suppression and note potential difficulty recognizing or managing immune-related hepatotoxicity in this setting.18
  • PMID 30655020: This letter describes a metastatic mismatch repair-deficient ACC case with low or normalized cortisol levels on mitotane that achieved a partial and ongoing response to pembrolizumab after prior chemotherapy, while noting severe immune-related hepatitis. The authors suggest MMR deficiency and lower steroid exposure may be associated with better checkpoint inhibitor responsiveness.19
  • PMID 31745526: A small retrospective case series of six patients with metastatic ACC reported clinical benefit from pembrolizumab combined with mitotane after prior mitotane-based therapy failure, with two partial responses and four cases of stable disease, alongside immune-related toxicities and exploratory biomarker observations.30
  • PMID 31777292: A cross-cancer analysis found that adrenocortical carcinoma had a lower-than-predicted objective response to immune checkpoint inhibitors relative to treatment-related adverse events. The authors suggest this may relate to frequent hormone excess, especially cortisol excess, and sparse tumor-infiltrating lymphocytes in ACC.14
  • PMID 32449531: A case of Lynch syndrome-associated, mismatch repair-deficient metastatic ACC showed durable remission after only two doses of nivolumab plus ipilimumab, despite treatment cessation for severe multiorgan immune-related toxicity. The report supports checkpoint blockade as a potentially effective option in selected biomarker-defined ACC.17
  • PMID 32468513: This review summarizes early experience with immune checkpoint inhibitors in advanced ACC, finding variable but sometimes durable activity, particularly with pembrolizumab, alongside generally manageable toxicity. Across reported studies, no validated predictive biomarker of response was identified, and elevated liver enzymes were the most common treatment-related adverse event.12
  • PMID 32474412: In ACC, tumor-infiltrating CD4+ and CD8+ T cells were associated with better survival, while glucocorticoid excess correlated with lower T-helper cell infiltration and particularly poor outcomes when combined with low TILs. The findings support hypercortisolism as a plausible contributor to variable checkpoint inhibitor benefit and suggest steroidogenesis inhibition as a strategy to test prospectively.6
  • PMID 32714316: A pan-cancer transcriptomic analysis reported that in ACC, tumors with high immune cell infiltration had better prognosis than low-infiltration tumors, contrasting with several other cancer types. The study supports prognostic relevance of the ACC immune microenvironment but does not test ACC-specific immunotherapy outcomes.4
  • PMID 32857613: This editorial summarizes early immune checkpoint inhibitor experience in advanced ACC, finding modest overall activity with occasional partial responses and stable disease but short median progression-free survival. It highlights cortisol hypersecretion as a possible negative predictive factor and notes that MSI, PD-L1, and tumor-infiltrating lymphocyte measures have not clearly predicted benefit.13
  • PMID 33552963: A pan-cancer TCGA analysis reported that high CMTM6 expression was associated with worse overall survival in adrenocortical carcinoma. The study frames CMTM6 as an immune-microenvironment and PD-L1 regulatory biomarker with potential relevance to immunotherapy, although ACC-specific mechanistic or treatment-response data were not provided.21
  • PMID 33918733: This review describes ACC as an immune-depleted tumor in which low leukocyte infiltration, altered antigen-presentation and death-receptor signaling, glucocorticoid-associated immune suppression, and other microenvironmental features may contribute to the modest activity of current immune checkpoint therapies. It also highlights candidate immune biomarkers and targets such as tumor-infiltrating lymphocytes and CD276.1
  • PMID 34086600: In ACC, cortisol-producing tumors showed broad suppression of immune-related gene expression, depletion of T-cell and NK/NKT-cell infiltrates, and enrichment of neutrophils despite higher tumor mutation burden. In vitro, cortisol impaired NK-cell activation and tumor killing, while glucocorticoid receptor antagonism with relacorilant restored these functions, supporting investigation of GR blockade with immune checkpoint inhibition.7
  • PMID 34194394: In TCGA-based ACC analyses, low-steroid phenotype tumors showed greater immune cell infiltration and higher expression of immune modulators including PD-L2, while both low- and high-steroid phenotypes overexpressed CD276. The study suggests steroid phenotype may help select immunotherapy strategies and supports reducing steroidogenesis before immune-based treatment.15
  • PMID 34664400: Computational profiling of TCGA ACC found that cortisol-secreting tumors have a broadly immunosuppressive microenvironment, including reduced expression of most immune-related genes and lower CD8 T-cell, activated NK-cell, and M1 macrophage infiltration. Cortisol secretion was associated with shorter disease-free survival, supporting hypercortisolism as a biologically plausible contributor to immunotherapy resistance.8
  • PMID 35372497: A pan-cancer bioinformatic study reported that Siglec-9 expression is downregulated in ACC versus normal tissue, varies across ACC molecular and immune subtypes, and is associated with better overall survival, disease-specific survival, and progression-free interval in ACC when expression is higher.22
  • PMID 35568842: A TCGA-based ACC analysis found generally low tumor mutational burden, no meaningful association between higher tumor mutational burden and immune-cell infiltration or TIDE score, and limited correlation with checkpoint expression. The study concludes tumor mutational burden has restricted value for predicting immune checkpoint inhibitor benefit in ACC.28
  • PMID 37746287: A case of ACC achieved a marked partial response to ipilimumab plus nivolumab, enabling subsequent R0 resection and short-term disease-free follow-up despite retained MMR protein expression. The report also summarizes that published ACC immunotherapy response rates are variable and that predictive biomarkers remain uncertain.36
  • PMID 37793855: In ACC, glucocorticoid receptor expression and a 34-gene glucocorticoid receptor activity signature were associated with higher tumor immune-cell infiltration and better survival, while glucocorticoid excess correlated with lower immune abundance and worse prognosis. The study suggests this signature may help stratify prognosis and identify patients more likely to benefit from immune checkpoint therapy.23
  • PMID 37928286: This case report describes MSI-high advanced ACC with local and metastatic recurrence showing a durable radiographic partial response and good tolerability during more than 15 months of pembrolizumab plus mitotane after poorly tolerated first-line EDP-mitotane. The authors argue that advanced ACC should be assessed for MSI-H/MMR deficiency to identify candidates for pembrolizumab.9
  • PMID 38235757: This review summarizes prospective and retrospective evidence for immune checkpoint inhibitors in advanced or progressive ACC after standard therapy failure. Pembrolizumab monotherapy produced overall response rates around 14% to 23%, with stable disease in a subset, while biomarker associations such as PD-L1 or MSI/MMR status remained inconsistent.2
  • PMID 38739542: This editorial summarizes that ACC is typically an immunologically cold tumor, with glucocorticoid excess, Wnt/beta-catenin activation, and TP53 alterations proposed as contributors to immune exclusion and limited checkpoint inhibitor benefit. It highlights reported PD-1, PD-L1, and CTLA-4 expression patterns, the association of PD-1 with longer progression-free survival and tumor-infiltrating T cells, and emerging strategies such as biomarker selection, MSI screening, glucocorticoid suppression, and vaccine combinations.5
  • PMID 39900383: A case of high-grade ACC with germline monoallelic MUTYH and POLE variants showed MSI-high status, elevated tumor mutation burden, and near-complete remission after 21 months of durvalumab plus tremelimumab. The report suggests DNA repair–related genomic features may identify an immunotherapy-responsive ACC subset.29
  • PMID 40570159: This study identifies serum GDF-15 as a potential biomarker of poor prognosis and reduced immune checkpoint inhibitor benefit in ACC, with lower baseline GDF-15 associated with better response and longer progression-free survival. Mitotane was linked to increased GDF-15, and high tumoural GDF-15 expression correlated with a less pro-inflammatory immune gene profile.24
  • PMID 40607488: This case report describes metastatic ACC with MSH6-deficient, MSI-H/dMMR status and Lynch syndrome showing marked clinical and radiologic response to pembrolizumab after mitotane intolerance and progression. The report also highlights genetic testing as clinically useful for identifying an immunotherapy-relevant subset and hereditary cancer risk.10
  • PMID 41650745: In ACC, mismatch repair deficiency was found in a minority of tumors and often occurred without microsatellite instability. In this cohort, dMMR was not associated with clinicopathologic features, prognosis, or improved immune checkpoint inhibitor response, although MMR immunohistochemistry remained useful for Lynch syndrome screening.11
  • PMID 41743178: A case of metastatic, cortisol-secreting ACC progressing after EDP-mitotane showed major regression after a single pembrolizumab dose despite microsatellite stability, low PD-L1 expression, and low tumor mutational burden, enabling later complete resection. The report highlights possible relevance of immune-related hepatitis, tumor immune infiltration, and prior cortisol control as response clues, while emphasizing biomarker uncertainty.20
  • PMID 38007705: A 2024 bioinformatic and single-cell study in lower-grade glioma identified APOBEC3C as an immune-associated prognostic marker linked to immune infiltration and checkpoint expression, and proposed it as a therapeutic target. Its relevance to ACC is indirect only, supporting caution when importing immune biomarker candidates from other cancers into ACC research.31
  • PMID 31233203: A mouse renal cortical adenocarcinoma study found that tumor-derived exosomes could stimulate antigen-specific CD8-positive T-cell cytotoxicity, enhanced by GM-CSF and IL-12 and linked to FasL/Fas signaling. Because the work was preclinical and performed in renal rather than adrenocortical carcinoma, its relevance to ACC is indirect and mainly conceptual.32
  • PMID 11531252: A population-based case-control study in non-transplant patients found that oral, but not inhaled, glucocorticoid use was associated with higher risk of non-melanoma skin cancer, especially squamous cell carcinoma. In this ACC note, the article is relevant only indirectly as supportive evidence that systemic glucocorticoids can impair immunosurveillance.16
  • PMID 33479027: A study in cutaneous squamous cell carcinoma found that CD8+CD103+ tissue-resident memory T cells could reflect reduced protective immunity rather than effective antitumor response. This indirect evidence adds nuance to ACC biomarker interpretation by emphasizing that immune-cell presence alone may not capture functional immune competence.25
  • PMID 34471502: A glioma study identified macrophage-related, especially M2-like, immune signatures associated with poorer survival and complex immunotherapy-related phenotypes. While not ACC-specific, it supports a more nuanced reading of immune infiltration markers by emphasizing myeloid composition and functional state.26
  • PMID 35937402: A pan-cancer TCGA bioinformatics study found that TLR-family expression generally correlated positively with immune and stromal scores and varied across immune subtypes, suggesting a link between innate immune signaling and tumor microenvironment state. Its ACC relevance is indirect, as the analysis was not designed to validate TLRs as ACC-specific biomarkers or predictors of checkpoint response.27
  • PMID 39742311: An Expression of Concern was issued for a prior ACC intratumoral microbiota study because part of its analysis relied on data from a retracted cancer microbiome paper, creating uncertainty around its conclusions and indicating that microbiome-based ACC signals should be treated cautiously pending re-analysis.34
  • PMID 41472277: A PBMC transcriptomic study in severe COVID-19 survivors identified persistent cancer-associated signatures and reported prognostic correlations in several cancers, including ACC. Its ACC relevance is indirect and mainly reinforces caution about extrapolating systemic or pan-cancer immune-state signals to ACC biomarker interpretation without tumor-specific validation.33

References

Footnotes

  1. Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success?. Cancers (Basel). 2021. PMID: 33918733. Local full text: 33918733.md ↩ ↩2 ↩3 ↩4

  2. Immunotherapy for endocrine tumours: a clinician’s perspective.. Endocr Relat Cancer. 2024. PMID: 38235757. Local full text: 38235757.md ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  3. The Expression and Prognostic Impact of Immune Cytolytic Activity-Related Markers in Human Malignancies: A Comprehensive Meta-analysis.. Front Oncol. 2018. PMID: 29515971. Local full text: 29515971.md ↩ ↩2 ↩3 ↩4

  4. Pan-Cancer Analysis of Immune Cell Infiltration Identifies a Prognostic Immune-Cell Characteristic Score (ICCS) in Lung Adenocarcinoma.. Front Immunol. 2020. PMID: 32714316. Local full text: 32714316.md ↩ ↩2 ↩3 ↩4

  5. Immune Checkpoint Molecules in Adrenocortical Carcinoma: Hope for Immunotherapy.. J Clin Endocrinol Metab. 2024. PMID: 38739542. Local full text: 38739542.md ↩ ↩2 ↩3 ↩4 ↩5

  6. Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma.. J Immunother Cancer. 2020. PMID: 32474412. Local full text: 32474412.md ↩ ↩2 ↩3 ↩4 ↩5

  7. Adrenal tumors provide insight into the role of cortisol in NK cell activity.. Endocr Relat Cancer. 2021. PMID: 34086600. Local full text: 34086600.md ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  8. Integrative computational immunogenomic profiling of cortisol-secreting adrenocortical carcinoma.. J Cell Mol Med. 2021. PMID: 34664400. Local full text: 34664400.md ↩ ↩2 ↩3 ↩4

  9. Durable response to pembrolizumab in microsatellite instability-high advanced adrenocortical carcinoma.. IJU Case Rep. 2023. PMID: 37928286. Local full text: 37928286.md ↩ ↩2 ↩3 ↩4 ↩5 ↩6

  10. An Excellent Clinical and Radiological Response Pattern to Pembrolizumab in a Patient With Metastatic Adrenocortical Carcinoma and Lynch Syndrome.. IJU Case Rep. 2025. PMID: 40607488. Local full text: 40607488.md ↩ ↩2 ↩3 ↩4

  11. Mismatch repair deficiency and microsatellite instability in adrenocortical carcinoma.. ESMO Open. 2026. PMID: 41650745. Local full text: 41650745.md ↩ ↩2 ↩3 ↩4 ↩5

  12. The role of immune checkpoint inhibitor therapy in advanced adrenocortical carcinoma revisited: review of literature.. J Endocrinol Invest. 2020. PMID: 32468513. Local full text: 32468513.md ↩ ↩2 ↩3 ↩4

  13. The long and winding road to effective immunotherapy in patients with adrenocortical carcinoma.. Future Oncol. 2020. PMID: 32857613. Local full text: 32857613.md ↩ ↩2 ↩3 ↩4

  14. Treatment-related adverse events and response rate to immune checkpoint inhibition.. J Int Med Res. 2020. PMID: 31777292. Local full text: 31777292.md ↩ ↩2

  15. Adrenocortical Carcinoma Steroid Profiles: In Silico Pan-Cancer Analysis of TCGA Data Uncovers Immunotherapy Targets for Potential Improved Outcomes.. Front Endocrinol (Lausanne). 2021. PMID: 34194394. Local full text: 34194394.md ↩ ↩2 ↩3 ↩4 ↩5

  16. Non-melanoma skin cancers and glucocorticoid therapy.. Br J Cancer. 2001. PMID: 11531252. Local full text: 11531252.md ↩ ↩2

  17. Sustained remission of Lynch syndrome-associated metastatic adrenocortical carcinoma following checkpoint inhibitor therapy-associated multiorgan autoimmunity.. Clin Endocrinol (Oxf). 2020. PMID: 32449531. Local full text: 32449531.md ↩ ↩2 ↩3

  18. Rapid disease progression in a patient with mismatch repair-deficient and cortisol secreting adrenocortical carcinoma treated with pembrolizumab.. Semin Oncol. 2018. PMID: 30262398. Local full text: 30262398.md ↩ ↩2

  19. Letter to Editor: Reply to R.T. Casey (Semin Oncol. 2018 Jun;45(3):151-155).. Semin Oncol. 2019. PMID: 30655020. Local full text: 30655020.md ↩ ↩2 ↩3

  20. Exceptional Response to a Single Dose of Pembrolizumab as Salvage Therapy for Metastatic Adrenocortical Carcinoma.. JCEM Case Rep. 2026. PMID: 41743178. Local full text: 41743178.md ↩ ↩2

  21. Prognostic Implications of Pan-Cancer CMTM6 Expression and Its Relationship with the Immune Microenvironment.. Front Oncol. 2020. PMID: 33552963. Local full text: 33552963.md ↩ ↩2

  22. Siglec-9, a Putative Immune Checkpoint Marker for Cancer Progression Across Multiple Cancer Types.. Front Mol Biosci. 2022. PMID: 35372497. Local full text: 35372497.md ↩ ↩2

  23. Discovery of a glucocorticoid receptor (GR) activity signature correlates with immune cell infiltration in adrenocortical carcinoma.. J Immunother Cancer. 2023. PMID: 37793855. Local full text: 37793855.md ↩ ↩2

  24. Mitotane treatment of adrenocortical carcinoma induces tumoural secretion of GDF-15: impact on poor prognosis and impaired responsiveness to immunotherapy.. Eur J Endocrinol. 2025. PMID: 40570159. Local full text: 40570159.md ↩ ↩2

  25. CD8+CD103+ tissue-resident memory T cells convey reduced protective immunity in cutaneous squamous cell carcinoma.. J Immunother Cancer. 2021. PMID: 33479027. Local full text: 33479027.md ↩ ↩2

  26. The molecular feature of macrophages in tumor immune microenvironment of glioma patients.. Comput Struct Biotechnol J. 2021. PMID: 34471502. Local full text: 34471502.md ↩ ↩2

  27. Comprehensive Bioinformatics Analysis of Toll-Like Receptors (TLRs) in Pan-Cancer.. Biomed Res Int. 2022. PMID: 35937402. Local full text: 35937402.md ↩ ↩2

  28. Tumor mutational burden presents limiting effects on predicting the efficacy of immune checkpoint inhibitors and prognostic assessment in adrenocortical carcinoma.. BMC Endocr Disord. 2022. PMID: 35568842. Local full text: 35568842.md ↩ ↩2

  29. Digenic Inheritance of Monoallelic MUTYH and POLE Germline Variants in Adrenocortical Carcinoma: Implications for Tumorigenesis and Immunotherapy.. Clin Genet. 2025. PMID: 39900383. Local full text: 39900383.md ↩ ↩2

  30. Response to Immunotherapy in Combination With Mitotane in Patients With Metastatic Adrenocortical Cancer.. J Endocr Soc. 2019. PMID: 31745526. Local full text: 31745526.md ↩ ↩2

  31. APOBEC3C is a novel target for the immune treatment of lower-grade gliomas.. Neurol Res. 2024. PMID: 38007705. Local full text: 38007705.md ↩ ↩2

  32. CD8+ T cells stimulated by exosomes derived from RenCa cells mediate specific immune responses through the FasL/Fas signaling pathway and, combined with GM‑CSF and IL‑12, enhance the anti‑renal cortical adenocarcinoma effect.. Oncol Rep. 2019. PMID: 31233203. Local full text: 31233203.md ↩ ↩2

  33. Long-Term Transcriptomic Reprogramming in Peripheral Blood Mononuclear Cells of Severe COVID-19 Survivors Reveals Pro-Oncogenic Signatures and Cancer-Associated Hub Genes.. Viruses. 2025. PMID: 41472277. Local full text: 41472277.md ↩ ↩2

  34. EXPRESSION OF CONCERN: Intratumoral Microbiota is Associated with Prognosis in Patients with Adrenocortical Carcinoma.. Imeta. 2024. PMID: 39742311. Local full text: 39742311.md ↩ ↩2

  35. Dendritic cells as potential adjuvant for immunotherapy in adrenocortical carcinoma.. Clin Endocrinol (Oxf). 2006. PMID: 16886963. Local full text: 16886963.md ↩

  36. Case Report: Response to ipilimumab and nivolumab in a patient with adrenocortical carcinoma.. Front Oncol. 2023. PMID: 37746287. Local full text: 37746287.md ↩

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