APOBEC-related mutagenesis and neo-peptide hydrophobicity: implications for response to immunotherapy
| Autor: | Pablo Tamayo, Timothy V. Pham, Amélie Boichard, Razelle Kurzrock, Igor F. Tsigelny, Garrett M. Frampton, Aaron M. Goodman, Scott M. Lippman, Huwate Yeerna |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
APOBEC lcsh:Immunologic diseases. Allergy medicine.medical_treatment In silico Cell Immunology Oncology and Carcinogenesis Mutagenesis (molecular biology technique) Biology medicine.disease_cause lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Immune system apobec neo-epitopes medicine Immunology and Allergy cancer Original Research Mutation Immunogenicity Immunotherapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health 030104 developmental biology medicine.anatomical_structure Oncology Mutagenesis 030220 oncology & carcinogenesis Cancer research immunotherapy lcsh:RC581-607 mutagenesis |
| Zdroj: | OncoImmunology, Vol 8, Iss 3 (2019) Oncoimmunology, vol 8, iss 3 Oncoimmunology |
| Popis: | Tumor-associated neo-antigens are mutated peptides that allow the immune system to recognize the affected cell as foreign. Cells carrying excessive mutation load often develop mechanisms of tolerance. PD-L1/PD-1 checkpoint immunotherapy is a highly promising approach to overcome these protective signals and induce tumor shrinkage. Yet, the nature of the neo-antigens driving those beneficial responses remains unclear. Here, we show that APOBEC-related mutagenesis – a mechanism at the crossroads between anti-viral immunity and endogenous nucleic acid editing – increases neo-peptide hydrophobicity (a feature of immunogenicity), as demonstrated by in silico computation and in the TCGA pan-cancer cohort, where APOBEC-related mutagenesis was also strongly associated with immune marker expression. Moreover, APOBEC-related mutagenesis correlated with immunotherapy response in a cohort of 99 patients with diverse cancers, and this correlation was independent of the tumor mutation burden (TMB). Combining APOBEC-related mutagenesis estimate and TMB resulted in greater predictive ability than either parameter alone. Based on these results, further investigation of APOBEC-related mutagenesis as a marker of response to anti-cancer checkpoint blockade is warranted. |
| Databáze: | OpenAIRE |
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