Dyckhoff Gerhard, Herold-Mende Christel, Scherer Sabine, Plinkert Peter K, Warta Rolf
Department of Otorhinolaryngology, Head and Neck Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
Division of Experimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, 69120 Heidelberg, Germany.
Cancers (Basel). 2022 Aug 7;14(15):3828. doi: 10.3390/cancers14153828.
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.
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.
HLA-A02 was the most prevalent allele in our cohort and was present in 51.1% of patients. The HLA-A25 and HLA-C06 alleles exhibited a significantly higher frequency in cancer patients than in the normal population of 174 blood and kidney donors ( = 0.02 and = 0.01, respectively, Fisher's exact test). For HLA-C04, a negative impact on overall survival in univariate analysis ( = 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, = 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; = 0.023).
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.
免疫反应的诱导和调节依赖于人类白细胞抗原（HLA）分子，该分子将源自突变新抗原或肿瘤相关抗原的肽呈递给细胞毒性T细胞。HLA分子的自然变异在肿瘤患者和正常人群中可能有所不同。因此，HLA等位基因频率与肿瘤患者的生存率之间可能存在关联。
在一组84例不同部位的头颈部鳞状细胞癌（HNSCC）患者中研究了这一问题。该队列随访超过10年。对血液样本进行1个字段水平的HLA-A/B/C CTS-PCR-SSP分型，并将结果与生存率相关联。
HLA-A02是我们队列中最常见的等位基因，51.1%的患者中存在该等位基因。与174名血液和肾脏供体的正常人群相比，HLA-A25和HLA-C06等位基因在癌症患者中的频率显著更高（分别为P = 0.02和P = 0.01，Fisher精确检验）。对于HLA-C04，单因素分析中对总生存有负面影响（P = 0.045），多因素分析中对生存有负面但无统计学意义的影响，提示生存较差（HR：1.82；95%CI：0.99 - 3.34，P = 0.053）。此外，多因素分析中HLA-A*02对总生存和无进展生存也有益（HR 0.54；95%CI：0.31 - 0.92；P = 0.023）。
HLA-A*02等位基因表达不仅可能预测更好的生存，还可能表明更好的肿瘤抗原呈递，从而有助于选择可能从依赖T细胞的免疫治疗中获益的患者。
