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Figure S6 from Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity

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posted on 2023-03-31, 00:22 authored by Pankaj Seth, Eva Csizmadia, Andreas Hedblom, Marta Vuerich, Han Xie, Mailin Li, Maria Serena Longhi, Barbara Wegiel

mRNA expression of activation markers and cytokines in CD8 T cells.

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American Heart Association

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ARTICLE ABSTRACT

Immunometabolism is emerging as a critical determinant of cancer pathophysiology. In this study, we explored the contributions of macrophage-expressed lactate dehydrogenase-A (LDH-A) to tumor formation in a K-Ras murine model of lung carcinoma. Myeloid-specific deletion of LDH-A promoted accumulation of macrophages with a CD86high and MCP-1high M1-like phenotype that suppressed tumor growth. This phenotypic effect was accompanied by reduced VEGF expression and angiogenesis, diminished numbers of PD-L1+ cancer cells, increased numbers of CD3+ T cells, and activation status of CD8+ T cells. Furthermore, it was associated with more pronounced antitumor T-cell immunity via induction of IL17 and IFNγ-producing CD8+ T (Tc17 and Tc1) cells, likely via suppression of lactate-driven PD-L1 expression. Our results suggest that expressions of LDH-A and lactate by macrophage in the tumor microenvironment are major drivers of T-cell immunosuppression, strongly supporting the concept of targeting stromal LDH-A as an effective strategy to blunt tumoral immune escape. Cancer Res; 77(13); 3632–43. ©2017 AACR.

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