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Thomas et al. J Transl Genet Genom 2024;8:249-77 Journal of Translational
DOI: 10.20517/jtgg.2024.15
Genetics and Genomics

Review Open Access

The reactive stroma response regulates the immune
landscape in prostate cancer

Rintu Thomas , John Michael Jerome, Kimiko L. Krieger, Naghmana Ashraf, David R. Rowley

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Correspondence to: Dr. David R. Rowley, Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor
Plaza, Houston, TX 77030, USA. E-mail: drowley@bcm.edu; Dr. Rintu Thomas, Department of Molecular and Cellular Biology,
Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. E-mail: Rintu.Thomas@bcm.edu
How to cite this article: Thomas R, Jerome JM, Krieger KL, Ashraf N, Rowley DR. The reactive stroma response regulates the
immune landscape in prostate cancer. J Transl Genet Genom 2024;8:249-77. https://dx.doi.org/10.20517/jtgg.2024.15

Received: 28 Mar 2024 First Decision: 12 Jun 2024 Revised: 10 Jul 2024 Accepted: 17 Jul 2024 Published: 24 Jul 2024

Academic Editor: Xiaolin Zi Copy Editor: Fangyuan Liu Production Editor: Fangyuan Liu

Abstract
Prostate cancer remains the most commonly diagnosed and the second leading cause of cancer-related deaths in
men in the United States. The neoplastic transformation of prostate epithelia, concomitant with modulations in the
stromal compartment, known as reactive stromal response, is critical for the growth, development, and progression
of prostate cancer. Reactive stroma typifies an emergent response to disrupted tissue homeostasis commonly
observed in wound repair and pathological conditions such as cancer. Despite the significance of reactive stroma in
prostate cancer pathobiology, our understanding of the ontogeny, phenotypic and functional heterogeneity, and
reactive stromal regulation of the immune microenvironment in prostate cancer remains limited. Traditionally
characterized to have an immunologically "cold" tumor microenvironment, prostate cancer presents significant
challenges for advancing immunotherapy compared to other solid tumors. This review explores the detrimental
role of reactive stroma in prostate cancer, particularly its immunomodulatory function. Understanding the
molecular characteristics and dynamic transcriptional program of the reactive stromal populations in tandem with
tumor progression could offer insights into enhancing immunotherapy efficacy against prostate cancer.

Keywords: Prostate cancer, emergent/repair biology, reactive stroma, tumor microenvironment, immune
landscape, immunotherapy

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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