Hsp70 modulates immune response in pancreatic cancer through dendritic cells

Bhuwan Giri, Prateek Sharma, Tejeshwar Jain, Anthony Ferrantella, Utpreksha Vaish, Siddharth Mehra, Bharti Garg, Srikanth Iyer, Vrishketan Sethi, Zoe Malchiodi, Rossana Signorelli, Harrys K.C. Jacob, John George, Preeti Sahay, Ejas P. Bava, Rajinder Dawra, Sundaram Ramakrishnan, Ashok Saluja, Vikas Dudeja

Research output: Contribution to journalArticlepeer-review

Abstract

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-α 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.

Original languageEnglish (US)
Article number1976952
JournalOncoImmunology
Volume10
Issue number1
DOIs
StatePublished - 2021

Keywords

  • Hsp70
  • Pancreatic cancer
  • dendritic cells
  • immunotherapy
  • stroma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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