Immune checkpoint inhibitor (ICI) therapy has successfully treated some cancer patients over the past decade. Several approaches have been tried to improve the therapeutic efficacy, such as combining ICIs and optimising timing and drug delivery routes. One research direction aims to enhance the efficacy and minimise the toxicity of ICI therapies by targeting drug delivery to the tumour-draining lymph node (TDLN). This approach is based on the TDLN being the first lymph node to encounter metastatic tumour cells and various tumour-derived factors, where both anti-tumour and immunosuppressive T cells can be induced. Accumulating evidence has shown that immunosuppressive T cells are activated in the TDLN before migrating to the tumour to perform their functions. The mechanism by which immunosuppressive T cells are induced in the TDLN remains unclear. While tumour-associated dendritic cells have been shown to induce immunosuppressive T cells in the TDLN, much less is known about whether other cell types in the TDLN communicate with and induce these immunosuppressive T cells. This project aimed to understand whether B cells regulate immunosuppressive T cells in the TDLN and their impact on ICI therapies. Using the E0771 breast cancer model, we observed that B cells were activated in the TDLN. However, in B cell-deficient mice (µMT), B cells did not impact E0771 tumour growth but substantially reduced the outcome of TDLN-targeted anti-PD-1 therapy. Further studies showed that immunosuppressive T cells were not induced in the TDLN in the absence of B cells. When we adoptively transferred B cells to µMT mice or depleted B cells using anti-CD20, only a small number of B cells were retained in the TDLNs. Despite this, immunosuppressive T cells were expanded in the TDLN and tumours responded to the anti-PD-1 therapy. Thus, our results suggest that B cells support immunosuppressive T cell expansion and are essential for the efficacy of TDLN-targeted anti-PD-1 therapy. Next, we attempted to understand how B cells induce immunosuppressive T cells in the TDLN. Since interleukin-10 (IL-10) is a well-characterised regulatory B cell (BReg) function, we adoptively transferred IL-10-/- B cells to µMT mice. We found that this approach did not abrogate the immunosuppressive T cells in the TDLN, suggesting that the effect is not dependent on the expression of IL-10. Alternatively, we wanted to identify the subpopulation of B cells that may support immunosuppressive T cell expansion. After B cells are activated, they can rapidly become IgM+ plasma cells to secrete low-affinity antibodies. Then, they go through a germinal centre reaction to differentiate into IgG plasma cells to produce high-affinity antibodies. IgM+ plasma cells have been recently reported as having regulatory functions. A notable observation in µMT mice that received wild-type (WT) B cell transfers was the recovery of IgM+ plasma cells but not IgG1+ plasma cells in the TDLNs. IgM+ plasma cells have been reported to be potent immunoregulatory B cells. Since B cell-mediated lymphotoxin signalling is essential for plasma cell differentiation, we transferred lymphotoxin alpha-deficient (LTα-/-) B cells to µMT mice and found this transfer abrogated both IgM+ and IgG1+ plasma cells. Furthermore, WT, but not LTα-/- B cells transfer, restored the response to anti-programmed cell death protein 1 (PD-1) therapy in µMT mice. Together, our results indicate IgM+ plasma cells are a subset of BRegs that can induce immunosuppressive T cells and augment anti-PD-1 therapeutic responses in the TDLN. Further studies are warranted to fully characterise IgM+ plasma cells and understand their role in cancer immunoregulation in the TDLN. This will provide valuable insight as to whether IgM+ plasma cells can be a potential target to augment TDLN-targeted ICI therapy.