In the Phase 2 CITYSCAPE trial, Tiragolumab, an anti-TIGIT antibody, demonstrated efficacy when combined with Atezolizumab, an anti-PD-L1, compared to Atezolizumab alone for the treatment of non-small cell lung carcinoma. In mouse models, inhibition of both the TIGIT and PD-1 pathways was shown to synergistically function to reinvigorate T cell function in the tumor microenvironment. However, the molecular and cellular mechanism of this protection remained unknown until now. A recent study published in Nature, co-supervised by Namrata Patil’s group and Robert Johnston from Genentech Inc., shed light on this mystery. Using mouse models and preclinical data, their group showed that anti-TIGIT treatment activates monocytes and macrophage antigen-presenting capacities, not only in the TME but also in the peripheral blood. This was dependent on FcγR engagement. The FcγR-anti-TIGIT engagement by myeloid cells promoted the shift from an exhausted phenotype towards a CD8 memory-like state program in the tumor microenvironment. Additionally, it blunted the expression of Treg suppressive markers in Tregs. This work reveals a positive role in FcγR engagement by anti-TIGIT antibodies and opens new avenues to increase binding not only to their antigen but also to enhance capacities for FcR binding.
The full article, published 28 February 2024 in Nature, is available with subscription here.
Review written by:
PhD candidate Eugenio Contreras Castillo
Department of Cell Biology
Institute of Cellular Physiology (IFC)
National Autonomous University of Mexico (UNAM)
8RHF+62 Mexico City