MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells

Limagne, Emeric; Nuttin, Lisa; Thibaudin, Marion; Jacquin, Élise; Aucagne, Romain; Bon, Marjorie; Revy, Solène; Barnestein, Robby; Ballot, Elise; Truntzer, Caroline; Dérangère, Valentin; Fumet, Jean-David; Latour, Charlène; Rébé, Cédric; Bellaye, Pierre-Simon; Kaderbhai, Courèche-Guillaume; Spill, Aodrenn; Collin, Bertrand; Callanan, Mary; Lagrange, Aurélie; Favier, Laure; Coudert, B.; Arnould́, Laurent; Ladoire, Sylvain; Routy, Bertrand; Joubert, Philippe; Ghiringhelli, François

doi:10.1016/j.ccell.2021.12.009

Cited by 91 publications

(72 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…. [ 8 ] Biological analyses underline that chemotherapy in these models induces immunogenic cell death as expected. Despite induction of immunogenic cell death process, chemotherapy is unable to promote CXCL10 production at the tumor site and immune recruitment.…”

mentioning

confidence: 80%

MAPK signaling regulates the efficacy of chemoimmunotherapy

Ghiringhelli

2022

Molecular & Cellular Oncology

View full text Add to dashboard Cite

mentioning

confidence: 80%

MAPK signaling regulates the efficacy of chemoimmunotherapy

Ghiringhelli

2022

Molecular & Cellular Oncology

View full text Add to dashboard Cite

“…TLR9 not only triggers plasmacytoid dendritic cells to produce type I IFN and activate the polyclonal B cells through the myeloid differentiation primary response protein 88 (MYD88) and interferon-regulatory factor 7 (IRF7) signaling pathway, but also induces the production of inflammasome-related factors pro-interleukin-1β (pro-IL-1β) and NOD-, LRR- and pyrin domain-containing 3 (NLRP3) via NF-κB ( Honda et al, 2005 ; Zhang X. et al, 2014 ). According to a recent study, TLR9 can sense mitochondrial DNA during mitophagy, and induce C-X-C motif chemokine ligand 10 (CXCL10) expression and CD8 + T cell recruitment, which reveals a novel role of chemotherapy in the innate immune response ( Limagne et al, 2022 ).…”

Section: Nucleic Acid-sensing Pathways Connect Dna Damage To Innate I...mentioning

confidence: 99%

Nucleic Acid Sensing Pathways in DNA Repair Targeted Cancer Therapy

Xie

Luo

2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The repair of DNA damage is a complex process, which helps to maintain genome fidelity, and the ability of cancer cells to repair therapeutically DNA damage induced by clinical treatments will affect the therapeutic efficacy. In the past decade, great success has been achieved by targeting the DNA repair network in tumors. Recent studies suggest that DNA damage impacts cellular innate and adaptive immune responses through nucleic acid-sensing pathways, which play essential roles in the efficacy of DNA repair targeted therapy. In this review, we summarize the current understanding of the molecular mechanism of innate immune response triggered by DNA damage through nucleic acid-sensing pathways, including DNA sensing via the cyclic GMP-AMP synthase (cGAS), Toll-like receptor 9 (TLR9), absent in melanoma 2 (AIM2), DNA-dependent protein kinase (DNA-PK), and Mre11-Rad50-Nbs1 complex (MRN) complex, and RNA sensing via the TLR3/7/8 and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). Furthermore, we will focus on the recent developments in the impacts of nucleic acid-sensing pathways on the DNA damage response (DDR). Elucidating the DDR-immune response interplay will be critical to harness immunomodulatory effects to improve the efficacy of antitumor immunity therapeutic strategies and build future therapeutic approaches.

show abstract

“…Using the syngeneic Lewis lung cancer (LLC1) model, Limagne et al. 1 initially investigated the optimal chemotherapy treatment strategy to induce immunological cell death (ICD), aiming to identify combinations that might work best with ICB. Standard chemotherapy platinum-doublet regimens were tested and cisplatin/pemetrexed was found to induce the highest levels of ten validated ICD markers.…”

Section: Main Textmentioning

confidence: 99%

“…In summary, the study by Laminge et al 1 has shown that CXCL10 is critical for CD8 T cell recruitment and necessary to restore immune checkpoint blockade efficacy within cisplatin/pemetrexedtreated tumors. The authors demonstrate that addition of MEK inhibitor restored CXCL10 expression, which was accomplished via upregulation of the optineurin and TLR9 axis.…”

mentioning

confidence: 95%