An Immunomodulatory Gallotanin-Rich Fraction From Caesalpinia spinosa Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma.

Details

Serval ID
serval:BIB_A80580548E5B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
An Immunomodulatory Gallotanin-Rich Fraction From Caesalpinia spinosa Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma.
Journal
Frontiers in immunology
Author(s)
Lasso P., Gomez-Cadena A., Urueña C., Donda A., Martinez-Usatorre A., Romero P., Barreto A., Fiorentino S.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
11
Pages
584959
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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 <sup>+</sup> and CD8 <sup>+</sup> T cells; decrease in the number of suppressor myeloid cells; increase in PD-L1 expression; decrease in the frequency of CD8 <sup>+</sup> 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.
Keywords
P2Et extract, PD-L1, breast cancer, combined therapy, immunotherapy, melanoma, natural products
Pubmed
Web of science
Open Access
Yes
Create date
22/12/2020 10:51
Last modification date
12/01/2021 7:26
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