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Immunotherapy using immune checkpoint inhibitors (ICIs) has shown superior efficacy compared with conventional chemotherapy in certain cancer types, establishing immunotherapy as the fourth standard treatment alongside surgical intervention, chemotherapy, and radiotherapy. In cancer immunotherapy employing ICIs, CD8‐positive cytotoxic T lymphocytes are recognized as the primary effector cells. For effective clinical outcomes, it is essential that the targeted cancer cells express HLA class I molecules to present antigenic peptides derived from the tumor. However, cancer cells utilize various mechanisms to downregulate or lose HLA class I molecules from their surface, resulting in evasion from immune surveillance. Correlations between prognosis and the integrity of HLA class I molecules expressed by cancer cells have been consistently found across different types of cancer. This paper provides an overview of the regulatory mechanisms of HLA class I molecules and their role in cancer immunotherapy, with a particular emphasis on the significance of utilizing pathological tissues to evaluate HLA class I molecules expressed in cancer cells. [ABSTRACT FROM AUTHOR]

Major histocompatibility complex (MHC) genes (referred to as human leukocyte antigen or HLA in humans) are a key component of vertebrate immune systems, coding for proteins which present antigens to T‐cells. These genes are outstanding in their degree of polymorphism, with important consequences for human and animal health. The polymorphism is thought to arise from selection pressures imposed by pathogens on MHC allomorphs, which differ in their antigen‐binding capacity. However, the existing theory has not considered MHC selection in relation to the formation of immune memory. In this paper, we argue that this omission limits our understanding of the evolution of MHC polymorphism and its role in disease. We review recent evidence that has emerged from the massive research effort related to the SARS‐CoV‐2 pandemics, and which provides new evidence for the role of MHC in shaping immune memory. We then discuss why the inclusion of immune memory within the existing theory may have non‐trivial consequence for our understanding of the evolution of MHC polymorphism. Finally, we will argue that neglecting immune memory hinders our interpretation of empirical findings, and postulate that future studies focusing on pathogen‐driven MHC selection would benefit from stratifying the available data according to the history of infection (and vaccination, if relevant). [ABSTRACT FROM AUTHOR]