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.

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.

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

Grant support

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