Multifunctional T Lymphocytes Generated After Therapy With an Antitumor Gallotanin-Rich Normalized Fraction Are Related to Primary Tumor Size Reduction in a Breast Cancer Model

Abstract

Natural compounds are promising sources for anticancer therapies because of their multifunctional activity and low toxicity. Although the host immune response (IR) is clearly implicated in tumor control, the relationship between natural therapies and IR has not yet been elucidated. The present work evaluates IR induction after treatment with a gallotanninrich fraction from Caesalpinia spinosa (P2Et). Breast tumor 4T1 cells were used to evaluate antitumor properties and IR activation. Apoptosis and expression of immunogenic cell death (ICD) markers were assessed in vitro, whereas IR and postvaccination tumor evolution were assessed in vivo. P2Et fraction induced apoptotic cell death, displaying phosphatidylserine externalization and DNA fragmentation. ICD markers such as calreticulin, high-mobility group box 1 translocation from nuclei to cytoplasm, and ATP secretion were observed. Primary tumor control was improved by vaccination with P2Et-pretreated 4T1 cells (t-P2Et), yielding long-lasting ex vivo multifunctional CD4 + and CD8 + T lymphocytes (interleukin [IL]-2 + , tumor necrosis factor [TNF]-α + , interferon [IFN]-γ + ) that secrete IL-2, TNF-α, IL-4, IL-5, and IFN-γ after specific 4T1 cell stimulation. The present study constitutes the first demonstration of a long-lasting antitumor IR induction and primary tumor reduction induced by a complex natural fraction. These data reveal the potential use of this fraction as an adjuvant in breast cancer treatment.

Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model

“…20 However, this model did not allow us to determine the generation of tumor antigen-specific T cells. In the present study, we show that treatment with a standardized fraction obtained from a plant, confers protection against tumor growth in the B16 mouse melanoma model through DCs activation and the generation of an adaptive antigen-specific IR that increases the frequencies of CD8 + IFN- γ + T cells.…”

“…20 Briefly, cells were fixed with 0.25% formaldehyde for 5 min, washed and then stained with the primary anti-CRT antibody followed by the Alexa Fluor 488 secondary antibody and incubated for 30 min. The MFI of stained cells was assessed within the live gate population.…”

“…This fraction contains galloylquinic acid derivatives in high proportions as well as pentagalloylglucose and gallic acid-containing compounds (gallates) in lower proportions. 20 In a previous study we showed that the P2Et fraction has anti-tumor activity in the 4T1 mammary mouse tumor model and decreases the number of lung metastasis. 21 …”

Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer

“…However, XBP1 was recently demonstrated to impede ICD in metastatic colorectal cancer cells exposed to epidermal growth factor receptor blockers and chemotherapy (Pozzi et al, 2016). Plant-derived polyphenol fractions have also been shown to induce potent ICD and T cell-dependent anti-tumor activity in preclinical models of melanoma and breast cancer (Gomez-Cadena et al, 2016; Uruena et al, 2015), but whether ER stress response factors mediate these effects remains to be determined.…”

Follistatin‐like protein 1 contributes to dendritic cell and T‐lymphocyte activation in nasopharyngeal carcinoma patients by altering nuclear factor κb and Jun N‐terminal kinase expression

“…destroy circulating tumor cells. [34][35][36] The tetramer detection method uses a single MHC-peptide tetramer molecule to reveal TCR expression on the surface of cytotoxic T lymphocytes, resulting in their rapid detection by flow cytometry. 37 Our tetramer results demonstrated that FSTL1 enhanced the antigen-presenting ability of DCs, which agreed with the ELISpot test results.…”