B2m, short for β2-microglobulin, is an essential subunit of the major histocompatibility complex (MHC) class I. It plays a crucial role in presenting tumor antigens to T cells, thus being significant in tumorigenesis and immune control. The gene is also involved in pathways related to immune response and cell-surface antigen presentation [1,2].

Knocking out B2M in murine models has provided insights into its role in cancer immunotherapy. In three murine models with different baseline MHC class I expression and sensitivity to anti-programmed death receptor (PD-1) therapy, B2M-deficient tumors showed differential responses. MC38 and YUMMER2.1 without B2M responded to anti-PD-1 alone or with an IL2 agonist, mediated by CD4+ T cells and natural killer (NK) cells. The more aggressive B16 without B2M expression only partially responded to the IL2 agonist, dependent on NK cells. This indicates that in the absence of B2M, activation of CD4+ T cells and NK cells can mediate responses to PD-1 blockade therapy in murine models [2].

In conclusion, B2m is vital for antigen presentation and immune control. Studies using B2m knockout mouse models have revealed its significant role in cancer immunotherapy, especially in understanding how the immune system responds to tumors in the absence of B2m-associated MHC class I presentation. These findings contribute to our knowledge of immune evasion mechanisms in cancer and potential strategies to enhance immunotherapy efficacy.