Tigit-KO Mouse

Tigit, also known as T cell immunoglobulin and ITIM domain, is an inhibitory receptor expressed on lymphocytes. It interacts with ligands CD155 and CD112 expressed on antigen-presenting cells or tumour cells, down-regulating T cell and natural killer (NK) cell functions. Tigit is part of the immune checkpoint pathways and plays a crucial role in hindering the anti-tumour responses, affecting multiple steps of the cancer immunity cycle [1,2,3,4,6,7].

In mouse tumour models, dual blockade of TIGIT and PD-L1 significantly reduces neuroblastoma growth, with complete responses in vivo. Also, in non-small cell lung carcinoma (NSCLC) mouse models, the effectiveness of PD-1 or TIGIT inhibition was reduced in the absence of CD226, and full restoration of CD226 signaling, and optimal anti-tumour CD8+ T cell responses, requires blockade of TIGIT and PD-1 [5,9]. In another mouse tumour model, anti-TIGIT surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors, driving anti-tumour CD8+ T cells from an exhausted effector-like state to a more memory-like state [8].

In conclusion, Tigit is a key inhibitor in the anti-tumour immune response. Studies using mouse models have revealed its role in cancer, especially in neuroblastoma and NSCLC. Blocking Tigit, especially in combination with PD-1/PD-L1 blockade, shows promise in enhancing anti-tumour immunity, providing potential new strategies for cancer immunotherapy [5,8,9].

References:

1. Harjunpää, H, Guillerey, C. 2019. TIGIT as an emerging immune checkpoint. In Clinical and experimental immunology, 200, 108-119. doi:10.1111/cei.13407. https://pubmed.ncbi.nlm.nih.gov/31828774/

2. Chauvin, Joe-Marc, Zarour, Hassane M. . TIGIT in cancer immunotherapy. In Journal for immunotherapy of cancer, 8, . doi:10.1136/jitc-2020-000957. https://pubmed.ncbi.nlm.nih.gov/32900861/

3. Cai, Letong, Li, Yuchen, Tan, Jiaxiong, Xu, Ling, Li, Yangqiu. 2023. Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy. In Journal of hematology & oncology, 16, 101. doi:10.1186/s13045-023-01499-1. https://pubmed.ncbi.nlm.nih.gov/37670328/

4. Chu, Xianjing, Tian, Wentao, Wang, Ziqi, Zhang, Jing, Zhou, Rongrong. 2023. Co-inhibition of TIGIT and PD-1/PD-L1 in Cancer Immunotherapy: Mechanisms and Clinical Trials. In Molecular cancer, 22, 93. doi:10.1186/s12943-023-01800-3. https://pubmed.ncbi.nlm.nih.gov/37291608/

5. Wienke, Judith, Visser, Lindy L, Kholosy, Waleed M, van Noesel, Max M, Molenaar, Jan J. 2024. Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy. In Cancer cell, 42, 283-300.e8. doi:10.1016/j.ccell.2023.12.008. https://pubmed.ncbi.nlm.nih.gov/38181797/

6. Pescia, Carlo, Pini, Giuditta, Olmeda, Edoardo, Ferrero, Stefano, Lopez, Gianluca. 2023. TIGIT in Lung Cancer: Potential Theranostic Implications. In Life (Basel, Switzerland), 13, . doi:10.3390/life13041050. https://pubmed.ncbi.nlm.nih.gov/37109579/

7. Chiang, Eugene Y, Mellman, Ira. . TIGIT-CD226-PVR axis: advancing immune checkpoint blockade for cancer immunotherapy. In Journal for immunotherapy of cancer, 10, . doi:10.1136/jitc-2022-004711. https://pubmed.ncbi.nlm.nih.gov/35379739/

8. Guan, Xiangnan, Hu, Ruozhen, Choi, Yoonha, Johnston, Robert J, Patil, Namrata S. 2024. Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells. In Nature, 627, 646-655. doi:10.1038/s41586-024-07121-9. https://pubmed.ncbi.nlm.nih.gov/38418879/

9. Banta, Karl L, Xu, Xiaozheng, Chitre, Avantika S, Chiang, Eugene Y, Mellman, Ira. . Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses. In Immunity, 55, 512-526.e9. doi:10.1016/j.immuni.2022.02.005. https://pubmed.ncbi.nlm.nih.gov/35263569/