ScRNA-seq of immune cells in tumors or during EAE from Pglyrp1 KO and wildtype mice.

PGLYRP1 is highly co-expressed with known co-inhibitory molecules and might be a promising novel target for immunotherapy. Indeed, genetic deletion of PGLYRP1 in mice led to decreased tumor growth and an increased activation/effector phenotype in CD8+ T cells, suggesting an inhibitory function of PGLYRP1 in CD8+ T cells. Surprisingly, genetic deletion of PGLYRP1 strongly protected against experimental autoimmune encephalomyelitis (EAE), a model of autoimmune disease in the central nervous system (CNS). Pglyrp1-deficient myeloid cells had a defect in antigen-presentation and T cell activation, indicating that PGLYRP1 might act as a proinflammatory molecule in myeloid cells during autoimmunity. Our results highlight PGLYRP1 as a promising novel target for immunotherapy, that, when targeted, elicits a potent anti-tumor immune response while protecting against tissue inflammation and autoimmunity. To characterize the role of PGLYRP1 in immune cells during tumor progression, we profiled the leukocytes in the MC38-OVA tumor and lymph nodes from 2 wild type (WT) and 2 PGLYRP1 knockout (KO) mice. For each genotype and tissue origin, cells from 2 mice were hashtagged respectively, pooled, and then split into 2 channels for combined singlecell RNA- and TCR-sequencing. Similarly, to characterize the role of PGLYRP1 in EAE, we profiled leukocytes in the CNS from 3 WT and 3 KO mice. For each genotype, cells from 3 mice were hashtagged individually, pooled, and then split into 2 channels for combined single-cell RNA- and TCR-sequencing.