Il15-KO Mouse

Il15, Interleukin 15, is a member of the immunoregulatory cytokines family. It plays multiple crucial functions, including dictating T cell response, regulating tissue repair and B cell homing, modulating inflammation, and activating NK cells. Il15 is predominantly expressed by myeloid cells and has a unique mode of tightly regulated secretion and trans-presentation. It is involved in the IL-15 signaling pathway, which is of great significance in immunotherapy [3].

In cancer research, studies have shown that IL15 can enhance the antitumor properties of T cells. For example, glypican-3-specific CAR T cells co-expressing IL15 and IL21 have superior expansion and antitumor activity against hepatocellular carcinoma [1]. IL15 also synergizes with radiotherapy to reprogram the tumor immune contexture through a dendritic cell connection [2]. Additionally, exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer, and IL-15 super-agonist treatment can attenuate tumor growth [4]. In the combination immunotherapy of cancer, although IL15 monotherapy was ineffective, when combined with other agents like antibodies to CTLA-4 and PD-L1, it led to marked prolongation of survival in tumor-bearing mice [5].

In conclusion, Il15 is a key cytokine for immunotherapy. Its functions in promoting T-cell and NK-cell-mediated anti-tumor responses have been demonstrated in various in vivo models. These findings suggest potential applications of Il15-based therapies in cancer treatment, highlighting the importance of understanding the role of Il15 in the context of the immune response and disease [1,2,3,4,5].

References:

1. Batra, Sai Arun, Rathi, Purva, Guo, Linjie, Metelitsa, Leonid S, Heczey, Andras. 2020. Glypican-3-Specific CAR T Cells Coexpressing IL15 and IL21 Have Superior Expansion and Antitumor Activity against Hepatocellular Carcinoma. In Cancer immunology research, 8, 309-320. doi:10.1158/2326-6066.CIR-19-0293. https://pubmed.ncbi.nlm.nih.gov/31953246/

2. Pilones, Karsten A, Charpentier, Maud, Garcia-Martinez, Elena, Demaria, Sandra. 2020. IL15 synergizes with radiotherapy to reprogram the tumor immune contexture through a dendritic cell connection. In Oncoimmunology, 9, 1790716. doi:10.1080/2162402X.2020.1790716. https://pubmed.ncbi.nlm.nih.gov/32934886/

3. Patidar, Manoj, Yadav, Naveen, Dalai, Sarat K. 2016. Interleukin 15: A key cytokine for immunotherapy. In Cytokine & growth factor reviews, 31, 49-59. doi:10.1016/j.cytogfr.2016.06.001. https://pubmed.ncbi.nlm.nih.gov/27325459/

4. Kurz, Emma, Hirsch, Carolina Alcantara, Dalton, Tanner, Winograd, Rafael, Bar-Sagi, Dafna. 2022. Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer. In Cancer cell, 40, 720-737.e5. doi:10.1016/j.ccell.2022.05.006. https://pubmed.ncbi.nlm.nih.gov/35660135/

5. Waldmann, Thomas A, Dubois, Sigrid, Miljkovic, Milos D, Conlon, Kevin C. 2020. IL-15 in the Combination Immunotherapy of Cancer. In Frontiers in immunology, 11, 868. doi:10.3389/fimmu.2020.00868. https://pubmed.ncbi.nlm.nih.gov/32508818/