B2m, also known as beta2-microglobulin, is a crucial component of the major histocompatibility complex (MHC) class I molecule. It is essential for presenting tumor antigens to T cells, playing a significant role in tumorigenesis and immune control. Alterations in B2m can impact antigen presentation and are involved in various biological processes related to cancer immunotherapies [1,2,3].

In murine models, knocking out B2m in different cancer cell lines such as MC38, YUMMER2.1, and B16 led to varied responses to anti-PD-1 and IL2 agonist therapies. In MC38 and YUMMER2.1, responses were mediated by CD4+ T cells and natural killer (NK) cells, while in the more aggressive B16, the response was NK-cell-dependent [2]. In human melanoma biopsies, B2M LOH was enriched in non-responders to therapy and was associated with more frequent infiltration of activated NK cells [2].

In conclusion, B2m is vital for MHC-I-mediated antigen presentation and immune response. Gene knockout mouse models have revealed its complex role in cancer immunotherapies, especially in determining the response to immune checkpoint blockade therapies. Understanding B2m's function through these models provides insights into tumor immune escape mechanisms and potential strategies to enhance immunotherapy efficacy [2].