An Immunomodulatory Gallotanin-Rich Fraction From Caesalpinia spinosa Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma
| Autor: | Susana Fiorentino, Paola Lasso, Alena Donda, Alfonso Barreto, Pedro Romero, Amaia Martinez-Usatorre, Alejandra Gomez-Cadena, Claudia Urueña |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Frontiers in Immunology, Vol 11 (2020) Frontiers in immunology, vol. 11, pp. 584959 |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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