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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]

The CDC crossmatch test is being phased out in solid organ donor allocation, and standard luminex single antigen bead assays do not differentiate complement activating function of HLA antibodies. The current study investigated the LIFECODES C3d‐binding assay to determine if it could accurately predict actual T and B cell CDC results in a cohort of highly sensitised patients. Nineteen serum samples from different highly sensitised solid organ patients were crossmatched against cells from 62 unique donors, with 174 total T and B cell crossmatches performed. The sera also underwent SAB assay using OLI and LC platforms, and C3d‐binding assay. Complement activating ability of each unique HLA antibody specificity detected using SAB was assigned based on the actual CDC results, which was then used to determine the accuracy of the C3d‐binding assay. The C3d‐binding assay was found to be highly accurate, with sensitivity of 95%, specificity 89% and negative predictive value 97% for class I DSA and the T cell CDC crossmatch results. Furthermore, we found 100% accuracy for prediction of the complement activating function of HLA‐C antibodies. Negative predictive value of above 90% was also found for HLA class II DSA. C3d‐binding proved more accurate than virtual crossmatch alone to predict CDC results. This study confirms that the C3d‐binding assay predicts actual CDC crossmatch results accurately. In particular, the high negative predictive value of the C3d‐binding assay may be extremely useful to define HLA antibodies that do not activate complement in highly sensitised recipients. [ABSTRACT FROM AUTHOR]