James Lisa M, Georgopoulos Apostolos P
The HLA Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, 55417, USA.
Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
J Immunol Sci. 2022 Jun 29;6(2):25-35. doi: 10.29245/2578-3009/2022/2.1238.
The association of Human Leukocyte Antigen (HLA) with melanoma has been well documented. Similarly, the outcome of checkpoint blockade immunotherapy (CBI) in melanoma depends, to some extent, on the HLA genotype of the patient. Although specific favorable (or unfavorable) HLA alleles for CBI outcome for melanoma have been identified, there is currently no reliable way to predict a positive, neutral or negative melanoma CBI outcome for other alleles. Here we used an immunogenetic epidemiological approach to identify HLA alleles whose frequency is negatively (or positively) associated with melanoma prevalence (protective or susceptibility alleles, respectively). The findings demonstrated that, indeed, HLA alleles that are negatively associated with melanoma prevalence in the population have been associated with good CBI outcome at the individual level and, conversely, HLA alleles that are positively associated with melanoma prevalence have been associated with poor CBI outcome in individuals. Given this good prediction of CBI cancer immunotherapy by specific immunogenetically discovered HLA alleles, we used this epidemiologic immunogenetic approach to identify more HLA Class I and II alleles protective (or susceptibility) for melanoma which would thus be good predictors of CBI outcomes in those cancers. This is a new approach to successfully (a) identify HLA protective or susceptibility alleles for melanoma, and (b) use that information in anticipating outcomes in CBI cancer immunotherapy.
人类白细胞抗原（HLA）与黑色素瘤之间的关联已有充分记录。同样，黑色素瘤中检查点阻断免疫疗法（CBI）的结果在一定程度上取决于患者的HLA基因型。尽管已确定了黑色素瘤CBI结果的特定有利（或不利）HLA等位基因，但目前尚无可靠方法预测其他等位基因的黑色素瘤CBI结果为阳性、中性或阴性。在此，我们采用免疫遗传学流行病学方法来确定其频率与黑色素瘤患病率呈负相关（或正相关）的HLA等位基因（分别为保护性或易感性等位基因）。研究结果表明，事实上，在人群中与黑色素瘤患病率呈负相关的HLA等位基因在个体水平上与良好的CBI结果相关，反之，与黑色素瘤患病率呈正相关的HLA等位基因在个体中与不良的CBI结果相关。鉴于通过特定免疫遗传学发现的HLA等位基因对CBI癌症免疫疗法有良好预测性，我们利用这种流行病学免疫遗传学方法来确定更多对黑色素瘤具有保护作用（或易感性）的HLA I类和II类等位基因，因此这些等位基因将是这些癌症中CBI结果的良好预测指标。这是一种成功（a）识别黑色素瘤的HLA保护性或易感性等位基因，以及（b）利用该信息预测CBI癌症免疫疗法结果的新方法。
