CD20+FCRL4+B Cells Activate CD8+T Cells in an MHC-I Restricted Manner in Nasopharyngeal Carcinoma Anti-tumor Immunity

Introduction: Nasopharyngeal carcinoma (NPC) is a malignant tumor characterized by massive immune cell infiltration. However, the function and significance of B cells in NPC have been neglected. Exploring B cells and their interactions with other immune cells will provide deeper insights into the immune microenvironment of NPC and theories of immunotherapy.

Methods: We utilized single-cell sequencing data to unravel characteristic B cell subtypes of nasopharyngeal carcinoma (NPC). Subsequently, through immunofluorescence techniques and the establishment of a coculture system, we validated a subset of CD20+FCRL4+ B cells and CD8+ T cells, highlighting their potential MHC-I-based interactions.

Results: Our analysis revealed the presence of a subset of CD20+FCRL4+ B cells that may interact with CD8+ T cells through the MHC-I pathway. Furthermore, we noted a colocalized distribution of CD20+FCRL4+ B cells and CD8+ T cells in NPC. Additionally, in vitro experiments demonstrated that IFNγ played a pivotal role in enhancing the delivery of MHC class I-restricted epitope peptides by B cells. B cells pre-stimulated with HK-1 lysate and IFNγ, when co-cultured with T cells, can induce the proliferation of CD8+ T cells and the formation of immunological memory. Ultimately, this process mediates the cytotoxicity of CD8+ T cells against tumor cells, and this mechanism is dependent on MHC class I molecules. Significantly, we found a positive correlation between the infiltration level of CD20+FCRL4+ B cells and the expression of PD-1, as well as the response to anti-PD-1 therapy in NPC.

Conclusions: Overall, our study elucidates the potential anti-tumor mechanisms of CD20+FCRL4+ B cells and provides insights into their role in anti-PD-1 immunotherapy for NPC.