Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors
Mario M Soldevilla, Helena Villanueva, Naiara Martinez-Velez, Daniel Meraviglia-Crivelli, Marta M Alonso, Javier Cebollero, Ashwathi P Menon, Montserrat Puigdelloses, Fernando Pastor
In spite of the success of PD-1 blocking antibodies in the clinic their benefits are still restricted to a small fraction of patients. Immune-desert tumors and/or the highly immunosuppressive tumor milieu might hamper the success of PD-1/PD-L1 blocking therapies into a broader range of cancer patients. Although still under debate, there is a cumulative body of evidence that indicates B tumor-infiltrating lymphocytes are a good prognostic marker in most types of cancer, especially in those that form ectopic lymphoid tissue structures.
Taking this into account, we reason that the adoptive transfer of activated B lymphoblasts (ABL) in the tumor could be a feasible therapeutic approach to shift the immunosuppressive tumor microenvironment into an immune-permissive one. In this work we show the antitumor effect of ABL therapy in two different tumor models: colon carcinoma (CT26) and melanoma (B16/F10). The ABL transfer in the most relevant non-immunogenic B16/F10 melanoma model depicts synergism with anti-PD-1 antibody therapy. Furthermore, systemic antitumor immunity was detected in mice treated with PD-1 antibody/ABL combination which was able to reach distal metastatic lesions.
CITATION Oncoimmunology. 2018 Apr 9;7(8):e1450711. doi: 10.1080/2162402X.2018.1450711. eCollection 2018.