KEY TAKEAWAYS
- The study aimed to investigate the mechanism of TIM3-mediated CD8+ TIL exhaustion and its significance in DLBCL.
- Researchers noticed the pivotal role of the TIM3/Galectin-9 pathway in CD8+ TIL exhaustion and immune evasion in DLBCL, suggesting promising avenues for novel immunotherapy development; further investigation is ongoing.
Overexpression of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) correlates with CD8+ tumor-infiltrating lymphocyte (TIL) exhaustion in diffuse large B-cell lymphoma (DLBCL). However, the precise mechanism underlying TIM3-mediated CD8+TIL exhaustion in DLBCL remains elusive.
Qiqi Zhu and the team aimed to assess the potential pathway involved in TIM3-mediated CD8+TIL exhaustion and its relevance in DLBCL.
Researchers performed an inclusive analysis to investigate the expression of TIM3 and its correlation with CD8+TIL exhaustion in DLBCL. They utilized single-cell RNA sequencing and RNA sequencing to examine the key ligand of TIM3 and elucidate the potential pathway of TIM3-mediated CD8+TIL exhaustion.
Furthermore, the biological significance of the TIM3-related pathway in DLBCL was explored using RNA sequencing, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction data. Finally, the possible regulatory mechanism of the TIM3-related pathway in DLBCL was explored through single-cell RNA sequencing and RNA sequencing.
CD8+TILs, particularly those in a terminally exhausted state, prominently expressed TIM3 in DLBCL. Galectin-9, primarily expressed in M2 macrophages, served as the principal ligand of TIM3, inducing CD8+TIL exhaustion through the TIM3/Galectin-9 pathway. High TIM3/Galectin-9 enrichment correlated with an immunosuppressive tumor microenvironment, severe clinical manifestations, inferior prognosis, and poor response to CHOP-based chemotherapy in DLBCL.
Additionally, it could predict the clinical efficacy of immune checkpoint blockade therapy. Furthermore, the TIM3/Galectin-9 enrichment in DLBCL may be regulated by the IFN-γ signaling pathway.
The study concluded that the TIM3/Galectin-9 pathway exerts a critical influence on CD8+TIL exhaustion and immune evasion in DLBCL. These findings underscore the importance of further functional studies to elucidate this pathway’s mechanisms and its potential as a foundation for novel immunotherapeutic approaches in DLBCL.
The study was sponsored by the Scientific Research Startup Foundation for Doctor, North Sichuan Medical College, and the Scientific Research and Development Fund Project, North Sichuan Medical College.
Source: https://pubmed.ncbi.nlm.nih.gov/38369502/
Zhu Q, Yang Y, Chen K, et al. (2024). “Diffuse large B-cell lymphoma: the significance of CD8+ tumor-infiltrating lymphocytes exhaustion mediated by TIM3/Galectin-9 pathway”. J Transl Med. 2024 Feb 18;22(1):174. doi: 10.1186/s12967-024-05002-3. PMID: 38369502; PMCID: PMC10874540.
