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TNFSF9 Is Associated with Favorable Tumor Immune Microenvironment in Patients with Renal Cell Carcinoma Who Are Treated with the Combination Therapy of Nivolumab and Ipilimumab.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Jul 06; Vol. 25 (13). Date of Electronic Publication: 2024 Jul 06. - Publication Year :
- 2024
-
Abstract
- Combination therapy of nivolumab and ipilimumab (NIVO + IPI) for metastatic renal cell carcinoma (mRCC) has shown efficacy, but approximately 20% of patients experience disease progression in the early stages of treatment. No useful biomarkers have been reported to date. Therefore, it is desirable to identify biomarkers to predict treatment responses in advance. We examined the tumor microenvironment (TME)-related gene expression in mRCC patients treated with NIVO + IPI, between the response and non-response groups, using tumor tissues, before administering NIVO + IPI. In TME-related genes, TNFSF9 expression was identified as a candidate for the predictive biomarker. Its expression discriminated between the response and non-response groups with 88.89% sensitivity and 87.50% specificity (AUC = 0.9444). We further analyzed the roles of TNFSF9 in TME using bioinformatics from The Cancer Genome Atlas (TCGA) cohort. An adaptive immune response was activated in the TNFSF9 -high-expression tumors. Indeed, T follicular helper cells, plasma B cells, and tumor-infiltrating CD8 <superscript>+</superscript> T cells were increased in the tumors, which indicates the promotion of humoral immunity due to enhanced T-B interactions. However, as the number of regulatory T cells (Treg) increased in the tumors, the percentage of dysfunctional T cells also increased. This suggests that not only PD-1 but also CTLA-4 inhibition may have suppressed Treg activation and improved the therapeutic effect in the TNFSF9 high-expression tumors. Therefore, TNFSF9 may predict the therapeutic efficacy of NIVO + IPI for mRCC and allow more appropriate patient selection.<br />Competing Interests: Chia-Ling Wu and Yi-Hua Jan were employed by ACT Genomics, Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.
- Subjects :
- Humans
Male
Female
Middle Aged
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Aged
Biomarkers, Tumor
Gene Expression Regulation, Neoplastic drug effects
Tumor Microenvironment drug effects
Tumor Microenvironment immunology
Carcinoma, Renal Cell drug therapy
Carcinoma, Renal Cell pathology
Carcinoma, Renal Cell immunology
Carcinoma, Renal Cell metabolism
Ipilimumab administration & dosage
Ipilimumab therapeutic use
Nivolumab therapeutic use
Nivolumab administration & dosage
Kidney Neoplasms drug therapy
Kidney Neoplasms immunology
Kidney Neoplasms pathology
Kidney Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39000552
- Full Text :
- https://doi.org/10.3390/ijms25137444