Myeloid-instructed CD14+CD4+T cells within the tumor microenvironment are associated with TNF⍺ signaling and prolonged survival in non-small cell lung cancer

Abstract

AbstractImmune cells from the adaptive and innate immune systems coexist in the tumor immune microenvironment (TME) to mediate tumor cell immunosurveillance and prevent tumor relapse. Relapse-free survival after surgical resection is heterogeneous in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of non-small cell lung cancer. Yet, little is known about the composition and spatial organisation of the TME that could explain the different prognoses for lung cancer patients. Using spatial multi-omics analyses, we show that LUAD and LUSC have distinct TMEs and that neutrophil-enriched tumors are associated with worse survival, while the accumulation of myeloid-instructed CD14+T cells in the tumor core was associated with prolonged patient survival. CD14+CD4+T cells express prototypic markers of myeloid cells and were found to be clonally expanded tumor-specific activated T cells. TNFα signaling was activated in tumors with high infiltration of CD14+CD4+T cells in the tumor core. Our results demonstrate that innate immune cells impact adaptive immune cell activity to support the deployment of discrete T cell populations with anti-tumor activity.