| First Author | Seth P | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 13 | Pages | 3632-3643 |
| PubMed ID | 28446465 | Mgi Jnum | J:243124 |
| Mgi Id | MGI:5907754 | Doi | 10.1158/0008-5472.CAN-16-2938 |
| Citation | Seth P, et al. (2017) Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity. Cancer Res 77(13):3632-3643 |
| abstractText | 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 IFNgamma-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. (c)2017 AACR. |
