Masters of adaptation - Essay

Sep 23, 2026

Uploaded by Cipher

One of the greatest challenges to cancer therapy is tumor cell plasticity. Cancer cells can rapidly alter their phenotype to promote survival and evade immune cell attack, while the plasticity of other cells in the tumor microenvironment (including immune cells responding to diverse bodily threats) can be leveraged to further support tumor growth and progression. The essay examines mutual plasticity between cancer and immune cells, highlighting epithelial–mesenchymal plasticity in tumor cells and showing how this interplay drives tumor progression and can be therapeutically targeted.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Introduction

Tumor heterogeneity and plasticity affect the TiME

Tumor heterogeneity

OPEN ACCESS Citation: Rosenbaum SR, Fields KM, Ford HL (2025) Masters of adaptation: How cancer and immune cell plasticity mediates tumor progression. PLoS Biol 23(7): e3003301 . [https://doi.org/10.1371/journal.pbio.3003301](https://doi.org/10.1371/journal.pbio.3003301) Academic Editor: Yibin Kang, Princeton University, UNITED STATES OF AMERICA Published: July 15, 2025 Copyright: © 2025 Rosenbaum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work has been supported through grants from the NIH: R01CA301267 (HLF), K00CA245552 (SRR), and T32GM136444 (KMF) . The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Abbreviations: CAFs, cancer-associated ESSAY Masters of adaptation: How cancer and immune cell plasticity mediates tumor progression Sheera R. Rosenbaum1☯, Kaiah M. Fields1,2☯, Heide L. Ford1,2* 1 Department of Pharmacology, University of Colorado Anschutz Medical Campus (AMC), Aurora, Colorado, United States of America, 2 Molecular Biology Program, University of Colorado Anschutz Medical Campus (AMC), Aurora, Colorado, United States of America ☯ These authors contributed equally to this work. * [heide.ford@cuanschutz.edu](heide.ford@cuanschutz.edu) Abstract One of the greatest challenges to cancer therapy is tumor cell plasticity. Cancer cells can rapidly alter their phenotype to promote survival and evade immune cell attack, while the plasticity of other cells in the tumor microenvironment (such as immune cells, which need to be able to respond to a diverse range of bodily threats) can be leveraged to further promote tumor growth and progression. This Essay discusses the mutual plasticity of cancer and immune cells, with a focus on epithelial–mesenchymal plasticity in tumor cells, and explores how this interplay contributes to tumor progression and can be targeted therapeutically. Introduction Cancer is a complex disease that can be driven by, but also eliminated through, its continuous communication with the immune system. The immune surveillance hypothesis proposes that the immune system can detect and eliminate emerging tumors, but that tumors evade this surveillance through complex crosstalk with immune cells that results in tumor cell escape from the anti-tumor immune response [ 1] . During tumor development, selection pressures shape the cellular composition of the tumor immune microenvironment (TiME), giving rise to distinct tumor immune subtypes which can be broadly categorized as: immune-inflamed (also known as‘hot’; replete with anti-tumor T cells); immune-desert (also known as ‘cold’; lacking an active immune response); and immune-excluded/altered (immune cells are prevented from infiltrating) [2] ( Fig 1) . Multiple groups have defined immune hot/ cold tumor subtypes more precisely, characterizing these subtypes by enrichment of specific immune cells and immune cell activity [3–5], as well as by distinct patterns of gene expression [2 ,3] or by being specific to certain cancer types. Importantly, these categories are associated with varied responses to immunotherapy, with immuneinflamed and T-cell-enriched tumors showing the best responses [2] . Thus, identifying PLOS Biology | [https://doi.org/10.1371/journal.pbio.3003301](https://doi.org/10.1371/journal.pbio.3003301) July 15, 2025 1 / 26 fibroblasts; EMT, epithelial-to-mesenchymal transition; METs, macrophage extracellular traps; NETs, neutrophil extracellular traps; NK, natural killer; NSCLC, non-small cell lung cancer; TiME, tumor immune microenvironment; TNBC, triple negative breast cancer. the mechanisms that shape the TiME will be critical to inform imm

FAQs

What is tumor cell plasticity and why is it important for cancer therapy?

Tumor cell plasticity lets cancer cells rapidly change phenotype to promote survival and evade immune cell attack, undermining effective therapy.

How do immune cells contribute to tumor progression through plasticity?

Immune cells adapt their phenotype and behavior in response to tumor signaling, which can either support or hinder anti-tumor immune responses and thereby influence progression.

What role does epithelial–mesenchymal plasticity play in the interaction between cancer and immune cells?

The essay focuses on epithelial–mesenchymal transition (EMT) as a major cancer cell plasticity mechanism and explores how this interplay contributes to tumor progression.

Sep 23, 2026

Uploaded by Cipher