Programme of self-reactive innate-like T cell-mediated cancer immunity

To kill or not to kill – The role of the tumor microenvironment in shaping group 1 ILC functions

“…Interestingly, IL-15 expressing tumors seem to promote cytotoxicity in a broader range of immune cells, as cytotoxic g1 ILCs were associated with an enrichment of CD8 + T cells/ILTKCs, both in the PyMT model as well as in human CRC. These data argue in favor of a cytotoxic module of immune surveillance controlling IL-15-producing tumors [ 31 , 69 , 78 ]. Therefore, manipulation of the TME to induce IL-15 might prove to be a useful strategy for future anti-tumor therapies.…”

“…Using the MMTV-PyMT tumor model, the authors showed infiltration of precancerous lesions and tumors by three different populations with cytotoxic properties, TCRβ + T cells, TCRδ + T cells, and TCR - NK1.1 + NKp46 + innate lymphocytes, all of which express GzmB and share a similar transcriptome. Due to their innate properties, the infiltrating T cells were termed “innate-like T cells with high cytotoxic potential” (ILTCK) [ 31 , 69 ]. The identified TCR - NK1.1 + NKp46 + innate lymphocyte population, referred to as type 1-like ILCs (ILC1ls) in this study, differs from intILC1 described by Gao et al ., as they express CD49a and CD103 while being largely negative for CD49b [ 31 , 62 ].…”

“…The dependency of this phenomenon on cell contact emphasizes once more that tumor cells might directly induce a cytotoxic phenotype in g1 ILCs. Intriguingly, both murine ILC1ls in the PyMT model and human Lin - CD56 + CD127 - CD7 + CD45RO + cells in CRC are accompanied by a clear enrichment of CD8 + ILTKCs with high killing potential, pointing towards an overarching program of innate-like tumor cytotoxicity possibly governed by tumor-derived IL-15 and additional signals [ 31 , 69 , 78 ].…”

Cancer Resistance to Immunotherapy: Molecular Mechanisms and Tackling Strategies

“…Their expansion and effector differentiation are dependent on IL-15, which is produced by many cancer cells; interestingly, inducible activation of IL-15 signaling in adoptively transferred ILTCK progenitors suppresses tumor growth while deletion of IL-15 in cancer cells increases tumor growth. The T cell subset is far more durable than typical killer T cells because PD-1 is not produced in by ILTCKs making them a potential target for immune cell-based therapy [ 173 ].…”

The New T Cell Subset Opens a New Realm for Tumor Immunotherapy

“…We speculated whether lymphocytes that can eliminate cancer cells on a broad spectrum existed. Chou and collaborators 4 described a population of αβ T cell receptor (TCR)-positive FCER1G-expressing innate-like T cells with high cytotoxic potential (ILTCKs). This finding suggests a potential immune response approach for tumor elimination, which increased our interest.…”