Hsp70 modulates immune response in pancreatic cancer through dendritic cells.

Autor:	Giri B; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Sharma P; Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA., Jain T; Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA., Ferrantella A; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Vaish U; Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA., Mehra S; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Garg B; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Iyer S; Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA., Sethi V; Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA., Malchiodi Z; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Signorelli R; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Jacob HKC; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., George J; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Sahay P; Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA., Bava EP; Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA., Dawra R; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Ramakrishnan S; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Saluja A; DeWitt Daughtry Family Department of Surgery, University of Miami, Coral Gables, FL, USA., Dudeja V; Division of Surgical Oncology, Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2021 Sep 18; Vol. 10 (1), pp. 1976952. Date of Electronic Publication: 2021 Sep 18 (Print Publication: 2021).
DOI:	10.1080/2162402X.2021.1976952
Abstrakt:	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. (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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