<i>PIEZO1</i>Deletion in CD11b+ Cells Suppresses Rhabdomyosarcoma Tumor Rejection and Generates a Tumor-Permissive Immune Landscape

Abstract In several cancers, including the aggressive sarcoma, rhabdomyosarcoma (RMS), tumor-associated myeloid cells (TAMCs) are largest immune populations and correlated with poor survival outcomes. TAMCs a mixed ‘plastic’ population that can sense changes in their environment, intra-tumoral ECM stiffness, change functioning accordingly. Despite clinical influences these have detrimental effects elevated tumor microenvironment (TME) stiffness has on cells’ phenotype, little is known about proteins mediate changes. We propose inhibition of mechanosensitive cation channel, PIEZO1, promotes pro-tumor phenotype while its activation skews this to anti-tumor thereby enhancing rejection.PIEZO1’s influence rejection was assessed by inoculating novel murine CD11b-conditional homozygous PIEZO1 knockout strain syngeneic RMS performing analyses. Tumor volume analyses found RMS-bearing KO mice developed larger tumors had diminished overall as compared wild-type mice. Flow cytometric analysis revealed increased macrophage frequency expansion MDSCs TME tumor-draining lymph node (TDLN). Interestingly, despite having T cells, they lowerPD-1+ CD4 CD8 cell frequencies; trend also observed spleen TDLN. These findings suggest without expression, predominantly polarize ‘pro-tumor’ state, preventing adaptive activation, leading lower burden. NCI T32 (5T32CA059366-27)