Human Leucocyte Antigens as Prognostic Markers in Head and Neck Squamous Cell Carcinoma

Simple Summary Human leucocyte antigens (HLAs) play a crucial role in the immune defense by presenting antigens to T lymphocytes. The particular combination of HLA alleles determines a patient-specific presentation of cell-derived peptide fragments to the patrolling immune cells. Since deregulated protein expression and mutations are hallmarks of cancer, such abnormal peptides can be presented by tumor cells and eventually recognized, and the presenting tumor cells are then killed by T cells. Therefore, the HLA composition might influence the formation and fate of cancer and might differ between tumor patients and healthy individuals. We performed HLA typing of 84 patients with head and neck cancer, and the results were compared to survival. Two of fifty HLA alleles analyzed showed a significantly different frequency compared with the normal population (HLA-A*25 and HLA-C*06). Patients with HLA-C*04 had poorer oncological outcomes, while patients with HLA-A*02 had significantly better survival. Background: The induction and regulation of immune responses depend on human leucocyte antigen (HLA) molecules that present peptides derived from mutated neoantigens or tumor-associated antigens to cytotoxic T cells. The natural variation of HLA molecules might differ between tumor patients and the normal population. Thus, there might be associations between the frequencies of HLA alleles and the survival of tumor patients. Methods: This issue was studied in a cohort of 84 patients with head and neck squamous cell carcinomas (HNSCCs) of different localizations. The cohort was followed up for more than 10 years. HLA-A/B/C CTS-PCR-SSP typing at 1 field level from blood samples was performed, and the results were correlated with survival. Results: HLA-A*02 was the most prevalent allele in our cohort and was present in 51.1% of patients. The HLA-A*25 and HLA-C*06 alleles exhibited a significantly higher frequency in cancer patients than in the normal population of 174 blood and kidney donors (p = 0.02 and p = 0.01, respectively, Fisher's exact test). For HLA-C*04, a negative impact on overall survival in univariate analysis (p = 0.045) and a negative, but statistically insignificant effect on survival toward poorer survival in multivariate analysis (HR: 1.82; 95% CI: 0.99-3.34, p = 0.053) were observed. In addition, HLA-A*02 was also beneficial for overall survival and progression-free survival in multivariate analysis (HR 0.54; 95% CI: 0.31-0.92; p = 0.023). Conclusion: HLA-A*02 allele expression might not only predict better survival but might also indicate superior tumor antigen presentation and, thus, help to select patients who could benefit from T-cell-dependent immunotherapies.

Automated summary

The specific combination of HLA alleles can affect the outcome and survival rate of cancer patients, with HLA-C*04 showing a negative impact on tumor outcomes and HLA-A*02 significantly improving survival rates.