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Journal Articles Immunity Year : 2013

Anticancer Chemotherapy-Induced Intratumoral Recruitment and Differentiation of Antigen-Presenting Cells

Sandy Adjemian
Stephen R Mattarollo
  • Function : Author
Heng Yang
  • Function : Author
João Paulo Portela catani
  • Function : Author
Dalil Hannani
Kim Steegh
  • Function : Author
Isabelle Martins
Frederic Schlemmer
  • Function : Author
Mickaël Michaud
  • Function : Author
Oliver Kepp
Abdul Qader Sukkurwala
  • Function : Author
Laurie Menger
  • Function : Author
Erika Vacchelli
Lorenzo Galluzzi
Philip R Taylor
  • Function : Author
Peter Van endert
  • Function : Author
Eric Solary
Mark J Smyth
  • Function : Author

Abstract

The therapeutic efficacy of anthracyclines relies on antitumor immune responses elicited by dying cancer cells. How chemotherapy-induced cell death leads to efficient antigen presentation to T cells, however, remains a conundrum. We found that intra-tumoral CD11c + CD11b + Ly6C hi cells, which displayed some characteristics of inflammatory dendritic cells and included granulomonocytic precursors, were crucial for anthracycline-induced anticancer immune responses. ATP released by dying cancer cells recruited myeloid cells into tumors and stimulated the local differentiation of CD11c + CD11b + Ly6C hi cells. Such cells efficiently engulfed tumor antigens in situ and presented them to T lymphocytes, thus vaccinating mice, upon adoptive transfer, against a challenge with cancer cells. Manipulations preventing tumor infiltration by CD11c + CD11b + Ly6C hi cells, such as the local overexpression of ectonu-cleotidases, the blockade of purinergic receptors, or the neutralization of CD11b, abolished the immune system-dependent antitumor activity of anthracyclines. Our results identify a subset of tumor-infiltrating leukocytes as therapy-relevant antigen-presenting cells.

Dates and versions

hal-02047416 , version 1 (06-03-2019)

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Yuting Ma, Sandy Adjemian, Stephen R Mattarollo, Takahiro Yamazaki, Laetitia Aymeric, et al.. Anticancer Chemotherapy-Induced Intratumoral Recruitment and Differentiation of Antigen-Presenting Cells. Immunity, 2013, 38 (4), pp.729-741. ⟨10.1016/j.immuni.2013.03.003⟩. ⟨hal-02047416⟩
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