Antitumor adaptive immunity remains intact following inhibition of autophagy and antimalarial treatment.

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  • Additional Information
    • Affiliation:
      Department of Pathology and Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California, USA
    • Subject Terms:
    • Subject Terms:
    • Abstract:
      The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy. However, our current understanding of the interplay between autophagy and the immune response remains incomplete. Here, we have evaluated how autophagy inhibition impacts the antitumor immune response in immune-competent mouse models of melanoma and mammary cancer. We observed equivalent levels of T cell infiltration and function within autophagy-competent and -deficient tumors, even upon treatment with the anthracycline chemotherapeutic doxorubicin. Similarly, we found equivalent T cell responses upon systemic treatment of tumor-bearing mice with antimalarial drugs. Our findings demonstrate that antitumor adaptive immunity is not adversely impaired by autophagy inhibition in these models, allowing for the future possibility of combining autophagy inhibitors with immunotherapy in certain clinical contexts.
    • Journal Subset:
      Biomedical; USA
    • Instrumentation:
      Clinical Decision Making in Nursing Scale (CDMNS) (Jenkins)
      Defining Issues Test (DIT) (Rest)
    • ISSN:
      0021-9738
    • MEDLINE Info:
      PMID: 27775547 NLM UID: 7802877
    • Grant Information:
      T32 AI007334/AI/NIAID NIH HHS/United States; R01 CA188404/CA/NCI NIH HHS/United States
    • Publication Date:
      20170903
    • Publication Date:
      20180924
    • Accession Number:
      http://dx.doi.org/10.1172/JCI85705
    • Accession Number:
      120006374
  • Citations
    • ABNT:
      STAROBINETS, H. et al. Antitumor adaptive immunity remains intact following inhibition of autophagy and antimalarial treatment. Journal of Clinical Investigation, [s. l.], v. 126, n. 12, p. 4417–4429, 2016. Disponível em: . Acesso em: 13 nov. 2019.
    • AMA:
      Starobinets H, Ye J, Broz M, et al. Antitumor adaptive immunity remains intact following inhibition of autophagy and antimalarial treatment. Journal of Clinical Investigation. 2016;126(12):4417-4429. doi:10.1172/JCI85705.
    • APA:
      Starobinets, H., Ye, J., Broz, M., Barry, K., Goldsmith, J., Marsh, T., … Debnath, J. (2016). Antitumor adaptive immunity remains intact following inhibition of autophagy and antimalarial treatment. Journal of Clinical Investigation, 126(12), 4417–4429. https://doi.org/10.1172/JCI85705
    • Chicago/Turabian: Author-Date:
      Starobinets, Hanna, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, and Jayanta Debnath. 2016. “Antitumor Adaptive Immunity Remains Intact Following Inhibition of Autophagy and Antimalarial Treatment.” Journal of Clinical Investigation 126 (12): 4417–29. doi:10.1172/JCI85705.
    • Harvard:
      Starobinets, H. et al. (2016) ‘Antitumor adaptive immunity remains intact following inhibition of autophagy and antimalarial treatment’, Journal of Clinical Investigation, 126(12), pp. 4417–4429. doi: 10.1172/JCI85705.
    • Harvard: Australian:
      Starobinets, H, Ye, J, Broz, M, Barry, K, Goldsmith, J, Marsh, T, Rostker, F, Krummel, M & Debnath, J 2016, ‘Antitumor adaptive immunity remains intact following inhibition of autophagy and antimalarial treatment’, Journal of Clinical Investigation, vol. 126, no. 12, pp. 4417–4429, viewed 13 November 2019, .
    • MLA:
      Starobinets, Hanna, et al. “Antitumor Adaptive Immunity Remains Intact Following Inhibition of Autophagy and Antimalarial Treatment.” Journal of Clinical Investigation, vol. 126, no. 12, Dec. 2016, pp. 4417–4429. EBSCOhost, doi:10.1172/JCI85705.
    • Chicago/Turabian: Humanities:
      Starobinets, Hanna, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, and Jayanta Debnath. “Antitumor Adaptive Immunity Remains Intact Following Inhibition of Autophagy and Antimalarial Treatment.” Journal of Clinical Investigation 126, no. 12 (December 2016): 4417–29. doi:10.1172/JCI85705.
    • Vancouver/ICMJE:
      Starobinets H, Ye J, Broz M, Barry K, Goldsmith J, Marsh T, et al. Antitumor adaptive immunity remains intact following inhibition of autophagy and antimalarial treatment. Journal of Clinical Investigation [Internet]. 2016 Dec [cited 2019 Nov 13];126(12):4417–29. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=ccm&AN=120006374&custid=s6224580