Glutamine is essential for overcoming the immunosuppressive microenvironment in malignant salivary gland tumors
Shuting Cao, Yu‐Wen Hung, Yi-Chang Wang, Yiyin Chung, Yue Qi, Ching Ouyang, Xiancai Zhong, Weidong Hu, Alaysia Coblentz, Ellie Maghami, Zuoming Sun, Heng Lin, David K. Ann
Abstract
Rationale: Immunosuppression in the tumor microenvironment (TME) is key to the pathogenesis of solid tumors. Tumor cell-intrinsic autophagy is critical for sustaining both tumor cell metabolism and survival. However, the role of autophagy in the host immune system that allows cancer cells to escape immune destruction remains poorly understood. Here, we determined if attenuated host autophagy is sufficient to induce tumor rejection through reinforced adaptive immunity. Furthermore, we determined whether dietary glutamine supplementation, mimicking attenuated host autophagy, is capable of promoting antitumor immunity. Methods: A syngeneic orthotopic tumor model in Atg5 +/+ and Atg5 flox/flox mice was established to determine the impact of host autophagy on the antitumor effects against mouse malignant salivary gland tumors (MSTs). Multiple cohorts of immunocompetent mice were used for oncoimmunology studies, including inflammatory cytokine levels, macrophage, CD4 + , and CD8 + cells tumor infiltration at 14 days and 28 days after MST inoculation. In vitro differentiation and in vivo dietary glutamine supplementation were used to assess the effects of glutamine on Treg differentiation and tumor expansion.