Hsp70 modulates immune response in pancreatic cancer through dendritic cells

Heat shock protein 70 (Hsp70), a protein chaperone, is known to promote cell survival and tumor progression. However, its role in the tumor microenvironment (TME) is largely unknown. We specifically evaluated Hsp70 in the TME by implanting tumors in wild-type (WT) controls or Hsp70(-/-) animals, thus creating a TME with or without Hsp70. Loss of Hsp70 led to significantly smaller tumors; there were no differences in stromal markers, but interestingly, depletion of CD8 + T-cells abrogated this tumor suppressive effect, indicating that loss of Hsp70 in the TME affects tumor growth through the immune cells. Compared to WT, adoptive transfer of Hsp70(-/-) splenocytes exhibited greater antitumor activity in immunodeficient NSG and Rag 1(-/-) mice. Hsp70(-/-) dendritic cells showed increased expression of MHCII and TNF-alpha both in vitro and in vivo. These results suggest that the absence of Hsp70 in the TME inhibits tumors through increased dendritic cell activation. Hsp70 inhibition in DCs may emerge as a novel therapeutic strategy against pancreatic cancer.

Automated summary

The absence of Hsp70 in the tumor microenvironment inhibits tumor growth through immune cells, and Hsp70(-/-) dendritic cells inhibit tumor growth by enhancing the immune response.