Peripheral Blood Mononuclear Cells of Patients with Breast Cancer Can Be Reprogrammed to Enhance Anti-HER-2/neu Reactivity and Overcome Myeloid-derived Suppressor Cells

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 2013 Nov 8

PMID 24197563

Citations 16

Authors

Kyle K Payne

Christine K Zoon

Wen Wan

Khin Marlar

Rebecca C Keim

Mehrab Nasiri Kenari

A Latif Kazim

Harry D Bear

Masoud H Manjili

Affiliations

Soon will be listed here.

Abstract

Two major barriers in the immunotherapy of breast cancer include tumor-induced immune suppression and the establishment of long-lasting immune responses against the tumor. Recently, we demonstrated in an animal model of breast carcinoma that expanding and reprogramming tumor-sensitized lymphocytes, ex vivo, yielded T memory (Tm) cells as well as activated CD25+ NKT cells and NK cells. The presence of activated CD25+ NKT and NK cells rendered reprogrammed T cells resistant to MDSC-mediated suppression, and adoptive cellular therapy (ACT) of reprogrammed lymphocytes protected the host from tumor development and relapse. Here, we performed a pilot study to determine the clinical applicability of our protocol using peripheral blood mononuclear cells (PBMCs) of breast cancer patients, ex vivo. We show that bryostatin 1 and ionomycin combined with IL-2, IL-7, and IL-15 can expand and reprogram tumor-sensitized PBMCs. Reprogrammed lymphocytes contained activated CD25+ NKT and NK cells as well as Tm cells and displayed enhanced reactivity against HER-2/neu in the presence of MDSCs. The presence of activated NKT cells was highly correlated with the rescue of anti-HER-2/neu immune responses from MDSC suppression. Ex vivo blockade experiments suggest that the NKG2D pathway may play an important role in overcoming MDSC suppression. Our results show the feasibility of reprogramming tumor-sensitized immune cells, ex vivo, and provide rationale for ACT of breast cancer patients.

Citing Articles

Myeloid‑derived suppressor cells as targets of emerging therapies and nanotherapies (Review).

Kumar D, Da Silva V, Chaves N Med Int (Lond). 2024; 4(5):46.

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MDSCs in breast cancer: an important enabler of tumor progression and an emerging therapeutic target.

Liu H, Wang Z, Zhou Y, Yang Y Front Immunol. 2023; 14:1199273.

PMID: 37465670 PMC: 10350567. DOI: 10.3389/fimmu.2023.1199273.

Gr1 CD11b MHCII myeloid cells boost T cell anti-tumor efficacy.

Payne K, Aqbi H, Butler S, Graham L, Keim R, Wan W J Leukoc Biol. 2018; 104(6):1215-1228.

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Perspectives on Systems Modeling of Human Peripheral Blood Mononuclear Cells.

Sen P, Kemppainen E, Oresic M Front Mol Biosci. 2018; 4:96.

PMID: 29376056 PMC: 5767226. DOI: 10.3389/fmolb.2017.00096.

Expansion of T Cells with Interleukin-21 for Adoptive Immunotherapy of Murine Mammary Carcinoma.

Zoon C, Wan W, Graham L, Bear H Int J Mol Sci. 2017; 18(2).

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