Icos, also known as Inducible Co-Stimulator, is a member of the B7 family and an activating costimulatory immune checkpoint expressed on activated T cells [2,6]. It binds to its ligand ICOSL, which is expressed on antigen-presenting cells and somatic cells including tumour cells in the tumour microenvironment [6]. The Icos signaling pathway is involved in T cell activation, effector functions, and also in regulatory T cell-mediated suppressive activities. It endows regulatory T (Treg) cells with increased generation, proliferation, and survival abilities [1].

In cancer, the Icos/ICOSL axis has a dual role. In some malignancies, Icos activation might potentiate the effect of an inhibitory checkpoint blockade, while its neutralization could decrease the function of immunosuppressive Tregs and inhibit lymphoid tumor cells expressing Tfh markers [4]. In triple-negative breast cancer (TNBC), elevated ICOSL expression in tumor tissues correlated with poor survival prognosis. Icos-enhanced B7H3-CAR-T cells significantly inhibited TNBC tumor growth in vitro and in vivo, and could effectively eradicate metastases [5]. In oral squamous cell carcinoma, the percentage of Icos+ tumor-infiltrating lymphocytes was identified as an independent prognostic factor [7]. In transplantation, blockade of the Icos:B7RP-1 pathway showed variable results in modulating lymphocyte proliferation in vitro and prolonging graft survival in vivo [2]. In allergic diseases, the Icos/ICOS-L axis has a dual role during the development of multiple allergic diseases [3].

In conclusion, Icos plays a crucial role in immune regulation, especially in T cell-related functions. Its role in various diseases such as cancer, transplantation-related immune responses, and allergic diseases has been demonstrated through in vivo and functional studies. The understanding of Icos from these research models helps in exploring potential therapeutic strategies for these diseases.

References:

1. Li, Dan-Yang, Xiong, Xian-Zhi. 2020. ICOS+ Tregs: A Functional Subset of Tregs in Immune Diseases. In Frontiers in immunology, 11, 2104. doi:10.3389/fimmu.2020.02104. https://pubmed.ncbi.nlm.nih.gov/32983168/

2. Hodgson, Russell, Christiansen, Dale, Ierino, Francesco, Sandrin, Mauro. 2022. Inducible Co-Stimulator (ICOS) in transplantation: A review. In Transplantation reviews (Orlando, Fla.), 36, 100713. doi:10.1016/j.trre.2022.100713. https://pubmed.ncbi.nlm.nih.gov/35878486/

3. Zhang, Xueyan, Hu, Xianyang, Tian, Tengfei, Pang, Wenhui. 2021. The role of ICOS in allergic disease: Positive or Negative? In International immunopharmacology, 103, 108394. doi:10.1016/j.intimp.2021.108394. https://pubmed.ncbi.nlm.nih.gov/34922247/

4. Amatore, Florent, Gorvel, Laurent, Olive, Daniel. 2019. Role of Inducible Co-Stimulator (ICOS) in cancer immunotherapy. In Expert opinion on biological therapy, 20, 141-150. doi:10.1080/14712598.2020.1693540. https://pubmed.ncbi.nlm.nih.gov/31738626/

5. Cao, Lixue, Peng, Haojie, Chen, Yanzhen, Zhang, Hui, Chen, Xinxin. 2024. ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis. In Journal for immunotherapy of cancer, 12, . doi:10.1136/jitc-2024-010028. https://pubmed.ncbi.nlm.nih.gov/39532433/

6. Solinas, Cinzia, Gu-Trantien, Chunyan, Willard-Gallo, Karen. . The rationale behind targeting the ICOS-ICOS ligand costimulatory pathway in cancer immunotherapy. In ESMO open, 5, . doi:10.1136/esmoopen-2019-000544. https://pubmed.ncbi.nlm.nih.gov/32516116/

7. Kajikawa, Hitomi, Hirata, Michinari, Haruna, Miya, Uzawa, Narikazu, Wada, Hisashi. . Tumor-infiltrating ICOS+ Effector Regulatory T-Cells in Oral Squamous Cell Carcinoma as a Promising Biomarker for Prognosis and 'Hot' Tumor. In Anticancer research, 42, 2383-2393. doi:10.21873/anticanres.15717. https://pubmed.ncbi.nlm.nih.gov/35489733/