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PERSPECTIVE article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1428118

Targeting the Tumor Microenvironment to Improve Clinical Outcomes in Triple Negative Breast Cancer Patients and Bridge the Current Disparity Gap

Provisionally accepted
Malak Alharbi Malak Alharbi 1,2Arya M. Roy Arya M. Roy 1Jayasree Krishnan Jayasree Krishnan 1Pawel Kalinski Pawel Kalinski 1Song Yao Song Yao 1Shipra Gandhi Shipra Gandhi 1*
  • 1 Roswell Park Comprehensive Cancer Center, University at Buffalo, Buffalo, United States
  • 2 King Abdulaziz University, Jeddah, Makkah, Saudi Arabia

The final, formatted version of the article will be published soon.

    Triple negative breast cancer (TNBC) is a heterogenous disease that disproportionately affects Black women. TNBC outcomes among Black women are dismal secondary to multiple factors, such as poor healthcare accessibility resulting in delays in diagnosis, and aggressive disease biology in addition to a pro-tumor immune microenvironment (TME). Black women with breast cancer exhibit elevated levels of serum pro-inflammatory cytokines, and a pro-tumorigenic TME with higher immunosuppressive regulatory T cells (Tregs), M2 macrophages and exhausted CD8 + T cells. We have shown that the combined use of toll-like receptor 3 (TLR3) ligands with interferon-α (chemokine modulation: CKM) is able to enrich the tumor with CD8 + T cells, while not increasing immunosuppressive cells. Recent clinical trials have revealed the efficacy of immune checkpoint inhibitors (ICI) in rejuvenizing exhausted CD8 + T cells. We hypothesize that strategies to modulate the TME by enriching chemokines that attract CD8 + T cells followed by reversal of CD8 + T cell exhaustion (ICI), when added to standard treatment, could potentially improve clinical outcomes, and mitigate the racial disparities in TNBC outcomes between Black and White Women.

    Keywords: Triple negative breast cancer, Racial Disparities, Tumor Microenvironment, exhausted CD8 + T cells, TLR3 agonist

    Received: 05 May 2024; Accepted: 01 Jul 2024.

    Copyright: © 2024 Alharbi, Roy, Krishnan, Kalinski, Yao and Gandhi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shipra Gandhi, Roswell Park Comprehensive Cancer Center, University at Buffalo, Buffalo, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.