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

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.

Immunogenic cell death in cancer: concept and therapeutic implications

“…Similar to prophylactic vaccines against pathogens, ICD requires robust adjuvants to initiate adaptive immune responses [ 43 , 44 ]. Such adjuvants, which are commonly referred to as DAMPs, are fully endogenous to dying cells and are generally released or exposed on the plasma membrane as a consequence of pre-mortem cellular stress [ 45 ].…”

ATHENA: an independently validated autophagy-related epigenetic prognostic prediction model of head and neck squamous cell carcinoma

“…Despite recent breakthroughs in surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, the prognosis of HNSCC is still poor and the 5-year survival rate of HNSCC stagnates at about 50% [ 2 ]. In the past decades, great efforts have been made to carry out genetic [ 3 ], epigenetic [ 4 ], transcriptomic [ 5 ] and proteomic [ 6 ] studies of HNSCC survival, since effective biomarkers possess the capability to predict prognosis of the disease, and can help to diagnose disease in its early stage, which is essential to improve the overall survival of HNSCC. Therefore, a significant amount of HNSCC associated molecular biomarkers has emerged [ 7 ].…”