Autophagy induced by conventional chemotherapy mediates tumor cell sensitivity to immunotherapy

Rupal Ramakrishnan, Chun Huang, Hyun Il Cho, Mark Lloyd, Joseph Johnson, Xiubao Ren, Soner Altiok, Daniel Sullivan, Jeffrey Weber, Esteban Celis, Dmitry I. Gabrilovich

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Autophagy attenuates the efficacy of conventional chemotherapy but its effects on immunotherapy have been little studied. Here, we report that chemotherapy renders tumor cells more susceptible to lysis by CTL in vivo. Moreover, bystander tumor cells that did not express antigen were killed by CTL. This effect was mediated by transient but dramatic upregulation of the mannose-6-phosphate receptor (MPR) on the tumor cell surface. Antitumor effects of combined treatment related to the kinetics ofMPR upregulation and abrogation of this event abolished the combined effect of immunotherapy and chemotherapy. MPR accumulation on the tumor cell surface during chemotherapy was observed in different mouse tumor models and in patients with multiple myeloma. Notably, this effect was the result of redistribution of the receptor caused by chemotherapy-inducible autophagy. Together, our findings reveal one molecular mechanism through which the antitumor effects of conventional cancer chemotherapy and immunotherapy are realized.

Original languageEnglish (US)
Pages (from-to)5483-5493
Number of pages11
JournalCancer Research
Volume72
Issue number21
DOIs
StatePublished - Nov 1 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ramakrishnan, R., Huang, C., Cho, H. I., Lloyd, M., Johnson, J., Ren, X., Altiok, S., Sullivan, D., Weber, J., Celis, E., & Gabrilovich, D. I. (2012). Autophagy induced by conventional chemotherapy mediates tumor cell sensitivity to immunotherapy. Cancer Research, 72(21), 5483-5493. https://doi.org/10.1158/0008-5472.CAN-12-2236