1. An Immunomodulatory Gallotanin-Rich Fraction From Caesalpinia spinosa Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma
- Author
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Susana Fiorentino, Paola Lasso, Alena Donda, Alfonso Barreto, Pedro Romero, Amaia Martinez-Usatorre, Alejandra Gomez-Cadena, and Claudia Urueña
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,natural products ,T cell ,medicine.medical_treatment ,Immunology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,breast cancer ,combined therapy ,pd-l1 ,PD-L1 ,expression ,medicine ,melanoma ,cancer ,Immunology and Allergy ,Cytotoxic T cell ,breast ,antitumor ,biology ,pathway ,business.industry ,Melanoma ,blockade ,Immunotherapy ,medicine.disease ,immunoresistance ,030104 developmental biology ,medicine.anatomical_structure ,immune-response ,Cancer research ,biology.protein ,cells ,immunotherapy ,Antibody ,Animals ,Antibodies, Monoclonal/immunology ,Antineoplastic Agents/immunology ,B7-H1 Antigen/immunology ,Breast Neoplasms/immunology ,CD4-Positive T-Lymphocytes/immunology ,CD8-Positive T-Lymphocytes/immunology ,Caesalpinia/immunology ,Cell Line, Tumor ,Cell Proliferation/physiology ,Female ,Humans ,Hydrolyzable Tannins/immunology ,Immunity/immunology ,Immunologic Factors/immunology ,MCF-7 Cells ,Melanoma, Experimental/immunology ,Mice ,Mice, Inbred BALB C ,Mice, Inbred C57BL ,Plant Extracts/immunology ,Polyphenols/immunology ,P2Et extract ,business ,lcsh:RC581-607 ,CD8 ,030215 immunology - Abstract
PD-1/PD-L1 pathway plays a role in inhibiting immune response. Therapeutic antibodies aimed at blocking the PD-1/PD-L1 interaction have entered clinical development and have been approved for a variety of cancers. However, the clinical benefits are reduced to a group of patients. The research in combined therapies, which allow for a greater response, is strongly encouraging. We previously characterized a polyphenol-rich extract from Caesalpinia spinosa (P2Et) with antitumor activity in both melanoma and breast carcinoma, as well as immunomodulatory activity. We hypothesize that the combined treatment with P2Et and anti-PD-L1 can improve the antitumor response through an additive antitumor effect. We investigated the antitumor and immunomodulatory activity of P2Et and anti-PD-L1 combined therapy in B16-F10 melanoma and 4T1 breast carcinoma. We analyzed tumor growth, hematologic parameters, T cell counts, cytokine expression, and T cell cytotoxicity. In the melanoma model, combined P2Et and anti-PD-L1 therapy has the following effects: decrease in tumor size; increase in the number of activated CD4 + and CD8 + T cells; decrease in the number of suppressor myeloid cells; increase in PD-L1 expression; decrease in the frequency of CD8 + T cell expressing PD-1; improvement in the cytotoxic activity of T cells; and increase in the IFN γ secretion. In the breast cancer model, P2Et and PD-L1 alone or in combination show antitumor effect with no clear additive effect. This study shows that combined therapy of P2Et and anti-PD-L1 can improve antitumor response in a melanoma model by activating the immune response and neutralizing immunosuppressive mechanisms.
- Published
- 2020