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Published in: Cancer Immunology, Immunotherapy 11/2023

Open Access 22-09-2023 | Breast Cancer | Research

GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model

Authors: Juan A. Hernández-Aceves, Jacquelynne Cervantes-Torres, Diana Torres-García, Francisco J. Zuñiga-Flores, Osiris J. Patiño-Chávez, Jorge A. Peña Agudelo, José Eduardo Aguayo-Flores, Yonathan Garfias, Laura Montero-León, Laura Romero-Romero, Armando Pérez-Torres, Gladis Fragoso, Edda Sciutto

Published in: Cancer Immunology, Immunotherapy | Issue 11/2023

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Abstract

Breast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst clinical outcomes and with fewer therapeutic options than other types of breast cancer. GK-1 is a peptide that in the experimental model of the metastatic 4T1 breast cancer has demonstrated anti-tumor and anti-metastatic properties. Herein, GK-1 (5 mg/kg, i.v.) weekly administrated not only decreases tumor growth and the number of lung macro-metastases but also lung and lymph nodes micro-metastases. Histological analysis reveals that GK-1 reduced 57% of the intra-tumor vascular areas, diminished the leukemoid reaction's progression, and the spleens' weight and length. A significant reduction in VEGF-C, SDF-1, angiopoietin-2, and endothelin-1 angiogenic factors was induced. Moreover, GK-1 prevents T cell exhaustion in the tumor-infiltrating lymphocytes (TILs) decreasing PD-1 expression. It also increased IFN-γ and granzyme-B expression and the cytotoxic activity of CD8+ TILs cells against tumor cells. All these features were found to be associated with a better antitumor response and prognosis. Altogether, these results reinforce the potential of GK-1 to improve the clinical outcome of triple-negative breast cancer immunotherapy. Translation research is ongoing towards its evaluation in humans.
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Metadata
Title
GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model
Authors
Juan A. Hernández-Aceves
Jacquelynne Cervantes-Torres
Diana Torres-García
Francisco J. Zuñiga-Flores
Osiris J. Patiño-Chávez
Jorge A. Peña Agudelo
José Eduardo Aguayo-Flores
Yonathan Garfias
Laura Montero-León
Laura Romero-Romero
Armando Pérez-Torres
Gladis Fragoso
Edda Sciutto
Publication date
22-09-2023
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 11/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-023-03538-9

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