Characterization of the molecular mechanisms underlying antitumor immune responses and immune escape mechanisms has resulted in the development of more effective immunotherapeutic strategies, including
immune checkpoint inhibitor (ICI)
therapy. ICIs can induce durable responses in patients with advanced
cancer in a wide range of
cancer types, however, the majority of the patients fail to respond to this
therapy or develop resistance in the course of the treatment. Information about the molecular mechanisms underlying primary and acquired resistance is limited. Although HLA class I molecules are crucial in the recognition of
tumor antigens by cytotoxic T lymphocytes, only a few studies have investigated the role of their expression level on malignant cells in ICI resistance. To address this topic, utilizing immunohistochemical staining with
monoclonal antibodies (mAbs) we analyzed HLA class I expression level in pre-treatment and post-treatment
tumor samples from
melanoma patients treated with
ipilimumab. Twenty-nine
metastases removed from six patients were available for the study, including 18 pre-treatment and 11 post-treatment lesions. Compared to
metastases excised before
ipilimumab therapy, post-treatment lesions displayed a significantly lower HLA class I expression level on
melanoma cells; HLA class I downregulation was most marked in progressing
metastases from nonresponding patients. We also evaluated the level of infiltration by CD8+ T cells and NK cells but did not find consistent changes between pre- and post-treatment samples. Our results indicate the potential role of HLA class I downregulation as a mechanism of ICI resistance.