B lymphocytes can be activated to act as antigen presenting cells to promote anti-tumor responses

Abstract

Immune evasion by tumors includes several different mechanisms, including the inefficiency of antigen presenting cells (APCs) to trigger anti-tumor T cell responses. B lymphocytes may display a pro-tumoral role but can also be modulated to function as antigen presenting cells to T lymphocytes, capable of triggering anti-cancer immune responses. While dendritic cells, DCs, are the best APC population to activate naive T cells, DCs or their precursors, monocytes, are frequently modulated by tumors, displaying a tolerogenic phenotype in cancer patients. In patients with cervical cancer, we observed that monocyte derived DCs are tolerogenic, inhibiting allogeneic T cell activation compared to the same population obtained from patients with precursor lesions or cervicitis. In this work, we show that B lymphocytes from cervical cancer patients respond to treatment with sCD40L and IL-4 by increasing the CD80+CD86+ population, therefore potentially increasing their ability to activate T cells. To test if B lymphocytes could actually trigger anti-tumor T cell responses, we designed an experimental model where we harvested T and B lymphocytes, or dendritic cells, from tumor bearing donors, and after APC stimulation, transplanted them, together with T cells into RAG1-/- recipients, previously injected with tumor cells. We were able to show that anti-CD40 activated B lymphocytes could trigger secondary T cell responses, dependent on MHC-II expression. Moreover, we showed that dendritic cells were resistant to the anti-CD40 treatment and unable to stimulate anti-tumor responses. In summary, our results suggest that B lymphocytes may be used as a tool for immunotherapy against cancer.

Intratumoral immunoglobulin isotypes predict survival in lung adenocarcinoma subtypes

“…The positive influence of IgG1 TIBs in KRAS mut tumors could be explained by presentation of BCR-cognate tumor antigens to CD4 + T-cells. Considered alongside recent reports revealing the importance of antigen-specific B-cells as cognate antigen presenters [6, 7, 18, 62, 63], these results support the concept that therapeutic vaccination using whole proteins or their encoding genes (including KRAS mut ) [64] could more efficiently exploit the antigen-presentation machinery of cognate B-cells. The hypothesis that mutant KRAS peptide itself is among the involved antigenic targets is especially attractive since, in contrast to other neoantigens, the driver mutation is a sensitive component of tumor survival.…”

The B-Side of Cancer Immunity: The Underrated Tune

“…In addition, it has been shown that these CD40-activated B cells are not sensitive to the immunosuppressive microenvironment [92], and that they can efficiently reach secondary lymphoid organs when injected in vivo, where they can efficiently activate T cells [93]. The potential of these CD40-activated B cells have been tested and validated in vivo in models of Human papillomavirus 16 (HPV16) E6 and E7 expressing TC-1 tumor [94], B16-F10 melanoma, E.G7 lymphoma [95], 4T1 breast tumor metastasis [96], sarcoma [25] and in spontaneous non-Hodgkin’s lymphoma in dogs [97]. In conclusion, CD40-activated B cells represent an interesting tool in cancer immunotherapy, and further studies, including clinical trials, should be performed to confirm this potential.…”

Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

“…114,115) The use of pDNA encapsulating LNPs as an antitumor adjuvant was previously demonstrated. 116) Recently, there has been considerable interest in targeting B lymphocytes (or B cells) in the spleen. B cells not only produce antibodies and cytokines for fighting infections and inflammation, they can act as APCs for stimulating specific T cell production.…”