KEY TAKEAWAYS
- The study aimed to evaluate Galectin-1 as a potential biomarker for checkpoint IO combined with TKIs in RCC patients.
- Elevated galectin-1 predicted therapeutic resistance, shorter PFS, and CD8+ T cell dysfunction in RCC IO/TKI therapy.
In renal cell carcinoma (RCC), the integration of checkpoint inhibitor immunotherapy (IO) with tyrosine kinase inhibitors (TKIs) lacks a clinically established biomarker. Tumoral overexpression of Galectin-1, with its potential immune-regulating functions, remains notable.
Jiajun Wang and the team aimed to investigate Galectin-1’s utility as a biomarker for guiding checkpoint IO combined with TKIs in RCC patients.
RNA-sequencing was conducted in two cohorts of RCC patients undergoing IO/TKI combination therapy (ZS-MRCC, JAVELIN-101). Immunohistochemistry and flow cytometry were employed to assess immune cell infiltration and function within the RCC tumor microenvironment. Response and progression-free survival (PFS) were determined using RECIST criteria.
The analysis revealed that Galectin-1 expression was elevated in RCC with higher stage (P< 0.001) and grade (P< 0.001). Additionally, high galectin-1 levels were associated with non-responders to IO/TKI therapy (P= 0.047) and correlated with shorter PFS in both the ZS-MRCC cohort (P= 0.036) and JAVELIN-101 cohort (P= 0.005).
Multivariate Cox analysis identified galectin-1 as an independent predictor for PFS (HR 2.505; 95% CI 1.116-5.622; P= 0.026). In the tumor microenvironment, high galectin-1 levels were linked to a decrease in GZMB+ CD8+ T cells (Spearman’s ρ = -0.31, P= 0.05) and an increase in PD1+ CD8+ T cells (Spearman’s ρ = 0.40, P= 0.01).
Moreover, high galectin-1 tumors exhibited elevated numbers of regulatory T cells (P= 0.039) and fibroblasts (P= 0.011). A random-forest score (RFscore) was developed to predict IO/TKI therapy benefit, revealing that IO/TKI therapy was beneficial for low-RFscore patients (HR 0.489, 95% CI 0.358-0.669, P< 0.001) but not for high-RFscore patients (HR 0.875, 95% CI 0.658-1.163, P= 0.357).
The study concluded that elevated galectin-1 levels were associated with IO/TKI therapy resistance, reduced PFS, and CD8+ T cell dysfunction, suggesting that galectin-1 is a potential biomarker for patient selection in RCC treatment.
Research was funded by the Shanghai Sailing Program, National Natural Science Foundation of China (NSFC), China Urological Oncology Research Fund and Shanghai Municipal Health Commission.
Source: https://pubmed.ncbi.nlm.nih.gov/38545824/
Wang J, Zhang S, Wang Y, et al. (2024) “Effect of galectin-1 on prognosis and responsiveness of immune checkpoint plus tyrosine kinase inhibition in renal cell carcinoma.” Cancer Med. 2024 Apr;13(7):e7113. doi: 10.1002/cam4.7113. PMID: 38545824; PMCID: PMC10974699.
