Messing with Signal 1: How Perturbed MHC Class I Antigen Presentation Contributes to Cancer

The antigen presentation machinery processes proteins for presentation to T cells, thereby controlling activation of the adaptive cellular immune response. Perturbation of this machinery has been linked to the development of various diseases. This review describes the function of the Major Histocompatibility Complex class I antigen presentation machinery and highlights how its perturbation can lead to compromised immune function and disease progression in the context of cancer. We categorize these perturbations into four distinct mechanistic levels: peptide generation, peptide loading, MHC class I integrity, and epigenetic regulation. This enables an integrated view of their functional impact on immune recognition, supporting therapeutic efforts to target antigen presentation or exploit these alterations in cancer.