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- Title
Tumor-derived inducible heat-shock protein 70 (HSP70) is an essential component of anti-tumor immunity.
- Authors
Dodd, K; Nance, S; Quezada, M; Janke, L; Morrison, J B; Williams, R T; Beere, H M
- Abstract
The anti-apoptotic function and tumor-associated expression of heat-shock protein 70 (HSP70) is consistent with HSP70 functioning as a survival factor to promote tumorigenesis. However, its immunomodulatory activities to induce anti-tumor immunity predict the suppression of tumor growth. Using the Hsp70.1/3−/−(Hsp70−/−) mouse model, we observed that tumor-derived HSP70 was neither required for cellular transformation nor for in vivo tumor growth. Hsp70−/− murine embryonic fibroblasts (MEFs) were transformed by E1A/Ras and generated tumors in immunodeficient hosts as efficiently as wild-type (WT) transformants. Comparison of Bcr-Abl-mediated transformation of WT and Hsp70−/− bone marrow and progression of B-cell leukemogenesis in vivo revealed no differences in disease onset or survival rates, and Eμ-Myc-driven lymphoma in Hsp70−/− mice was phenotypically indistinguishable from that in WT Eμ-Myc mice. However, Hsp70−/− E1A/Ras MEFs generated significantly larger tumors than their WT counterparts in C57BL/6 J immune-competent hosts. Concurrent with this was a reduction in intra-tumoral infiltration of innate and adaptive immune cells, including macrophages and CD8+ T cells. Evaluation of several potential mechanisms revealed an HSP70-chemokine-like activity to promote cellular migration. These observations support a role for tumor-derived HSP70 in facilitating anti-tumor immunity to limit tumor growth and highlight the potential consequences of anti-HSP70 therapy as an efficacious anti-cancer strategy.
- Subjects
HSP70 heat-shock proteins; ANTINEOPLASTIC agents; CANCER immunology; APOPTOSIS; PROTEIN expression; IMMUNOSUPPRESSION; CELL transformation
- Publication
Oncogene, 2015, Vol 34, Issue 10, p1312
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/onc.2014.63