KEY TAKEAWAYS
- The study aimed to measure TIGIT positivity in RCC T cells to explore its role in immune resistance.
- Higher TIGIT expression in RCC may predict better response to TIGIT-targeting therapies.
Immune checkpoint inhibitors (ICI) have transformed renal cell carcinoma (RCC) treatment, yet many patients experience non-response or develop resistance. This highlights the urgent need for alternative immunomodulatory therapies. The co-inhibitory molecule T-cell immunoglobulin and ITIM domain (TIGIT) may contribute to resistance against current ICI and is being explored as a therapeutic target.
Oscar Perales and the team aimed to quantify TIGIT positivity in tumor-infiltrating T cells in RCC, investigating its potential role in resistance to ICI.
Researchers used tissue microarrays from primary RCC tumors, adjacent normal tissue, and RCC metastases to measure TIGIT in tumor-infiltrating CD3+ T cells via quantitative immunofluorescence. They compared TIGIT+ CD3+ levels in RCC with those in 4 other cancers: melanoma, non-small cell lung, cervical, and head and neck. This approach helped assess TIGIT expression across different tumor types for a broader understanding of its role in resistance.
The results indicated no significant differences in TIGIT positivity between primary RCC tumors and matching metastatic samples. TIGIT levels in RCC were similar to those in lung cancer but lower compared to melanoma, cervical, and head and neck cancers. Correlation analysis with previous patient-matched spatial proteomic data showed a negative association between TIGIT and the checkpoint proteins PD-1 and LAG3.
The study concluded that assessing TIGIT expression in T cells from primary or metastatic RCC specimens is crucial. Increased TIGIT positivity may indicate a higher likelihood of response to TIGIT-targeting antibody therapies.
The study was funded in part by the NIH.
Source: https://pubmed.ncbi.nlm.nih.gov/39105820/
Perales O, J ilaveanu L, Adeniran A, et al. (2024). “TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3.” Cancer Immunol Immunother. 2024 Aug 6;73(10):192. doi: 10.1007/s00262-024-03773-8. PMID: 39105820; PMCID: PMC11303630.
