TCRseq of Rpl18*-specific T cells from MC38 tumor and draining lymph node

The protein PI3K-interacting protein (PIK3IP1), or transmembrane inhibitor of PI3K (TrIP), is highly expressed by T cells and can modulate PI3K activity in these cells. Several studies have also revealed that TrIP is rapidly downregulated following T cell activation and can play important roles in T cell differentiation. We have generated mice with CD8-specific TrIP deficiency. Here we provide data detailing that activated TrIP KO CD8 T cells display an increased inflammatory transcriptional profile in the absence of TrIP. Consistent with these effects, we also show that knockout of TrIP specifically in CD8 T cells resulted in reduced growth of syngeneic tumors. When characterizing the tumor-infiltrating cells, we found that TrIP KO led to an increase in the number of tumor-infiltrating T cells, as well as a delay in the acquisition of an exhausted phenotype, based on phenotypic and transcriptomic analyses. Finally, our data suggest that TrIP regulates the diversity of T cell clonal responses to tumors, since we observed an increase in the number of distinct T cell clonotypes responding to a tumor neoantigen. Taken together, we show that TrIP intrinsically restricts the CD8 T cell response to tumors, and that targeting TrIP may augment the anti-tumor response in a way that is distinct from established checkpoint therapies. Tumor and tumor draining lymph nodes (TDLN) from WT and CD8-specific TrIP knockout mice were harvested 10 days after MC38 tumor injection. CD8+ Rpl18 Tetramer+ cells were sorted from both tissues and prepared for sequencing.