Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer

Erika Vacchelli, Lorenzo Galluzzi, Vanessa Rousseau, Alice Rigoni, Antoine Tesnière, Nicolas F. Delahaye, Frédéric Schlemmer, Laurie Menger, Abdul Qader Sukkurwala, Sandy Adjemian, Isabelle Martins, Mickaël Michaud, Ariane Dunant, Oliver Kepp, Elisabeth Brambilla, Jean Charles Soria, Laurence Zitvogel, Guido Kroemer

Research output: Contribution to journalArticlepeer-review

Abstract

The success of anticancer chemotherapy relies at least in part on the induction of an immune response against tumor cells. Thus, tumors growing on mice that lack the pattern recognition receptor TLR4 or the purinergic receptor P2RX7 fail to respond to chemotherapy with anthracyclins or oxaliplatin in conditions in which the same neoplasms growing on immunocompetent mice would do so. Similarly, the therapeutic efficacy (measured as progression-free survival) of adjuvant chemotherapy with anthracyclins is reduced in breast cancer patients bearing loss-of-function alleles of TLR4 or P2RX7. TLR4 loss-of-function alleles also have a negative impact on the therapeutic outcome of oxaliplatin in colorectal cancer patients. Here, we report that loss-of-function TLR4 and P2RX7 alleles do not affect overall survival in non-small cell lung cancer (NSCLC) patients, irrespective of the administration and type of chemotherapy. The intrinsic characteristics of NSCLC (which near-to-always is chemoresistant and associated with poor prognosis) and/or the type of therapy that is employed to treat this malignancy (which near-to-always is based on cisplatin) may explain why two genes that affect the immune response to dying cells fail to influence the clinical progression of NSCLC patients.

Original languageEnglish
Pages (from-to)271-278
Number of pages8
JournalOncoImmunology
Volume1
Issue number3
DOIs
Publication statusPublished - 2012

Keywords

  • Calreticulin
  • IALT
  • Immunogenic cell death
  • Necrosis factor α
  • Rs3751143
  • Rs4986790
  • Tumor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Oncology
  • Immunology

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