ArticleBMC endocrine disorders2022
Tumor mutational burden presents limiting effects on predicting the efficacy of immune checkpoint inhibitors and prognostic assessment in adrenocortical carcinoma.
Article in BMC endocrine disorders, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 32 citations in OpenAlex.
- Low-dose radiotherapy as an immunomodulator in cancer: dose-specific mechanisms and hybrid high-dose/low-dose strategies.Biomarker research · 2026Review
- Pseudo-Progression Observed During Immune Checkpoint Inhibitor Therapy for Advanced Adrenocortical Carcinoma.IJU case reports · 2026Article
- Adrenal tumor microenvironment: hormone-immune crosstalk, molecular heterogeneity, and immunotherapeutic opportunities.Frontiers in immunology · 2026Review
- ASCL2 contributes to clinical assessments of breast cancer and mediates tumor progression via the interaction with CLDN3.Scientific reports · 2025Article
- The expression of mercaptopyruvate sulfurtransferase serves as a potential biomarker for prognostic stratification and immunotherapy in certain cancers.Frontiers in oncology · 2025Article
- Frontiers in Systemic Therapy for Unresectable or Metastatic Adrenocortical Carcinoma: Harnessing Novel Therapeutic Approaches.Clinical Medicine Insights. Oncology · 2025Review
- Commentary: Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes.Frontiers in immunology · 2024Article
- Cancer Biomarkers and Precision Oncology: A Review of Recent Trends and Innovations.Clinical Medicine Insights. Oncology · 2024Review
- Establishing a predictive model for tumor mutation burden status based on CT radiomics and clinical features of non-small cell lung cancer patients.Translational lung cancer research · 2023Article
- Article
- Cuproptosis regulatory genes greatly contribute to clinical assessments of hepatocellular carcinoma.BMC cancer · 2023Article
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8 authors at 2 institutions in 1 country.
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Abstract
backgroundAdrenocortical carcinoma (ACC) is a highly malignant urologic cancer and tends to metastasize. Although immune checkpoint inhibitors (ICIs) bring a glimmer of light to conquer ACC, only a fraction of patients have benefit from ICIs treatment. It is well known that tumor mutational burden (TMB) is closely associated with the efficacy and response rate of immunotherapy. However, its roles in ACC were not investigated.
methodsUsing somatic mutations data of 92 ACC samples in TCGA database, we calculated their TMB values by the 'maftools' package in R software (Ver 3.6.3). To explore the roles of TMB in ICIs therapy, we have addressed this issue from three perspectives. First, the effects of TMB levels on tumor immune microenvironment (TIM) were analyzed through CIBERSORT algorithm, ssGSEA method and TIMER web server. Second, we investigated the expressive correlations between TMB level and five pivotal immune checkpoints based on Pearson coefficient. Third, the difference in TIDE score between high- and low-TMB groups was compared. The prognostic value of TMB was also evaluated. Besides, GSEA was performed to determine the changes in the activities of signaling pathways caused by TMB.
resultsTMB values in ACC samples were not high. The average of total mutation counts in each sample was only 21.5. High TMB could lead metabolic reprogramming and poor survival outcomes. However, it was unable to affect the infiltration levels of lymphocytes, and failed to facilitate the activities of immune-related pathways. Regarding immune checkpoints (ICs), only PD-L1 upregulation could result in a good prognosis, and TMB level did not correlate with the expressions of other ICs except for LAG3. There was no significant difference in TIDE score between high- and low-TMB groups. Combining the present results and previous study, we speculated that inadequate stimulation for neoantigens formation, intrinsic immune-resistance and special genomic alterations were three possible reasons for TMB limiting functions in TIM and ICIs. Besides, TMB was toughly applied in clinical practice due to its high cost of determination and non-universal definition of high TMB.
conclusionsTMB presents limiting effects on prediction for ICIs efficacy and prognostic assessment for ACC patients.
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