A loss-of-function polymorphism in ATG16L1 compromises therapeutic outcome in head and neck carcinoma patients

Julie Le Naour; Zsofia Sztupinszki; Vincent Carbonnier; Odile Casiraghi; Virginie Marty; Lorenzo Galluzzi; Zoltan Szallasi; Guido Kroemer; Erika Vacchelli

doi:10.1080/2162402X.2022.2059878

A loss-of-function polymorphism in ATG16L1 compromises therapeutic outcome in head and neck carcinoma patients

Oncoimmunology. 2022 Apr 17;11(1):2059878. doi: 10.1080/2162402X.2022.2059878. eCollection 2022.

Authors

Julie Le Naour^{1

2

3}, Zsofia Sztupinszki^{4

5

6}, Vincent Carbonnier^{1

2

3}, Odile Casiraghi⁷, Virginie Marty⁸, Lorenzo Galluzzi^{9

10

11}, Zoltan Szallasi^{4

5

6}, Guido Kroemer^{1

2

12

13}, Erika Vacchelli^{1

2}

Affiliations

¹ Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Institut Universitaire de France, Paris, France.
² Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
³ Université Paris Sud, Paris Saclay, Faculty of Medicine Kremlin Bicêtre, France.
⁴ Computational Health Informatics Program (CHIP), Boston Children's Hospital, Boston, MA, USA.
⁵ Harvard Medical School, Boston, MA, USA.
⁶ Danish Cancer Society Research Center, Copenhagen, Denmark.
⁷ Department of Head and Neck Surgical and Medical Oncology, Gustave Roussy Cancer Campus, Paris-Saclay University, Villejuif, France.
⁸ Experimental and Translational Pathology Platform (PETRA), AMMICa Inserm US23/UMS CNRS3655, Gustave Roussy Cancer Campus, Villejuif, France.
⁹ Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
¹⁰ Sandra and Edward Meyer Cancer Center, New York, NY, USA.
¹¹ Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA.
¹² Institut du Cancer Paris CARPEMAP-HP, Hôpital Européen Georges Pompidou, Pôle de Biologie, Paris, France.
¹³ Department of Cancer Medicine, Gustave Roussy Cancer Campus, Villejuif, France.

Abstract

The anticancer immune response is shaped by immunogenic cell stress and death pathways. Thus, cancer cells can release danger-associated molecular patterns that act on pattern recognition receptors expressed by dendritic cells and their precursors to elicit an antitumor immune response. Here, we investigated the impact of single nucleotide polymorphisms (SNPs) in genes affecting this cancer-immunity dialogue in the context of head and neck squamous cell carcinoma (HNSCC). We observed that homozygosity for a loss-of-function SNP (rs2241880, leading to the substitution of a threonine residue in position 300 by an alanine) affecting autophagy related 16 like 1 (ATG16L1) is coupled to poor progression-free survival in platinum-treated HNSCC patients. This result was obtained on a cohort of patients enrolled at the Gustave Roussy Cancer Campus and was validated on an independent cohort of The Cancer Genome Atlas (TCGA). Homozygosity in rs2241880 is well known to predispose to Crohn's disease, and epidemiological associations between Crohn's disease and HNSCC have been reported at the levels of cancer incidence and prognosis. We speculate that rs2241880 might be partially responsible for this association.

Keywords: FPR1; Immunogenic cell death; P2RX7; radiotherapy; toll-like receptor.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Autophagy-Related Proteins / genetics
Crohn Disease* / genetics
Head and Neck Neoplasms* / drug therapy
Head and Neck Neoplasms* / genetics
Humans
Polymorphism, Single Nucleotide
Squamous Cell Carcinoma of Head and Neck / drug therapy
Squamous Cell Carcinoma of Head and Neck / genetics
Treatment Outcome

Substances

ATG16L1 protein, human
Autophagy-Related Proteins

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.