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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1498942
This article is part of the Research Topic Community Series in Immune Responses Against Tumors - From the Bench to the Bedside: Volume II View all articles

Cryoablation of primary breast cancer tumors induces a systemic abscopal effect altering TIME (Tumor-Immune Micro-Environment) in distant tumors

Provisionally accepted
Flávia Sardela De Miranda Flávia Sardela De Miranda 1Dalia Martinez-Marin Dalia Martinez-Marin 2Rachel L. Babcock Rachel L. Babcock 1,2Maribel Castro Maribel Castro 1Geetha P. Boligala Geetha P. Boligala 2*Sonia Y. Khan Sonia Y. Khan 1,3*Kathryn L. Furr Kathryn L. Furr 1*Isabel Castro-Piedras Isabel Castro-Piedras 1Nicholas Wagner Nicholas Wagner 1*Dakota E. Robison Dakota E. Robison 1*Karla Daniele Karla Daniele 1*Sharda P. Singh Sharda P. Singh 1Kevin Pruitt Kevin Pruitt 2*Michael W. Melkus Michael W. Melkus 1*Rakhshanda L. Rahman Rakhshanda L. Rahman 1,4*
  • 1 Texas Tech University Health Sciences Center, Lubbock, United States
  • 2 University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • 3 The University of Texas Rio Grande Valley, Edinburg, Texas, United States
  • 4 MetroHealth Medical Center, Cleveland, Ohio, United States

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

    Despite recent advances, triple-negative breast cancer (TNBC) patients remain at high risk for recurrence and metastasis, which creates the need for innovative therapeutic approaches to improve patient outcomes. Cryoablation is a promising, less invasive alternative to surgical resection, capable of inducing tumor necrosis via freeze/thaw cycles. Necrotic cell death results in increased inflammatory signals and release of preserved tumor antigens, which have the potential to boost the local and systemic anti-tumor immune response. Thus, compared to surgery, cryoablation enhances the activation of T cells leading to an improved abscopal effect, defined as the occurrence of a systemic response after local treatment. We previously showed with a bilateraltumor mouse model of TNBC that cryoablation of the primary tumor leads to increased infiltration of distant tumors by tumor infiltrating lymphocytes (TILs) and decreased rates of recurrence and metastasis. However, the early drivers of the cryoablation-generated abscopal effect are still unknown and knowledge of the mechanism could provide insight into improving the anti-tumor immune response through pharmacologic immune modulation in addition to cryoablation. Here we show that cryoablation of mouse mammary carcinomas results in smaller distant tumors that harbor increased frequencies of anti-tumor cells [such as natural killer (NK) cells], accompanied by a systemic increase in the frequency of migratory conventional type 1 dendritic cells (cDC1; CD103 + XCR1 + ), compared to resection. The changes in cell frequencies are mirrored by the immune gene signature of the distant tumors, with cryoablation inducing genes involved with NK cell activation and leukocyte-mediated toxicity, including IL11ra1 and Pfr1. These results better define the early mechanisms through which cryoablation improves tumor elimination, which is mediated by enhanced frequencies of anti-tumoral cells such as NK and cDC1s at the distant tumor and in the spleen of mice treated with cryoablation, respectively.

    Keywords: breast cancer, Cryoablation, abscopal effect, RNA-seq analysis, immune response

    Received: 19 Sep 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Sardela De Miranda, Martinez-Marin, Babcock, Castro, Boligala, Khan, Furr, Castro-Piedras, Wagner, Robison, Daniele, Singh, Pruitt, Melkus and Rahman. 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:
    Geetha P. Boligala, University of North Carolina at Chapel Hill, Chapel Hill, 27599, North Carolina, United States
    Sonia Y. Khan, The University of Texas Rio Grande Valley, Edinburg, Texas, United States
    Kathryn L. Furr, Texas Tech University Health Sciences Center, Lubbock, United States
    Nicholas Wagner, Texas Tech University Health Sciences Center, Lubbock, United States
    Dakota E. Robison, Texas Tech University Health Sciences Center, Lubbock, United States
    Karla Daniele, Texas Tech University Health Sciences Center, Lubbock, United States
    Kevin Pruitt, University of North Carolina at Chapel Hill, Chapel Hill, 27599, North Carolina, United States
    Michael W. Melkus, Texas Tech University Health Sciences Center, Lubbock, United States
    Rakhshanda L. Rahman, Texas Tech University Health Sciences Center, Lubbock, United States

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