Cited by 32Cancer Immunotherapy and BiomarkersImmune cells in cancerCancer, Stress, Anesthesia, and Immune Response

Aerobic Exercise Alters the Melanoma Microenvironment and Modulates ERK5 S496 Phosphorylation

Open access
Savage, Hannah, Pareek, Sumedha, Lee, Jonghae, Ballarò, Riccardo, Conterno Minussi, Darlan, Hayek, Karma, Sadullozoda, Mumina, Lochmann, Brooke S. +9 more·2023·Cancer Immunology Research

Published version of a preprint

Abstract

Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a phenotypic shift in the tumor-associated macrophage population and increased the expression of MHC class II transcripts. We further demonstrated that ERK5 S496A knock-in mice, which are phosphorylation deficient at the S496 residue, “mimicked” the exercise effect when unexercised, yet when exercised, these mice displayed a reversal in the effect of exercise on tumor growth and macrophage polarization compared with wild-type mice. Taken together, our results reveal tumor-specific differences in the immune response to exercise and show that ERK5 signaling via the S496 residue plays a crucial role in exercise-induced tumor microenvironment changes. See related Spotlight by Betof Warner, p. 1158

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1158/2326-6066.cir-22-0465

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

2 of the 40 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [24]Huijbers EJM, Khan KA, Kerbel RS, & Griffioen AW (2022). Tumors resurrect an embryonic vascular program to escape immunity. Science Immunology, 7(67), 6388. 10.1126/SCIIMMUNOL.ABM6388/ASSET/DBFA8AF6-1395-4453-99BC-D9036AFA5994/ASSETS/IMAGES/LARGE/SCIIMMUNOL.ABM6388-F3.JPG 35030032 · DOI

Cited by

Sorted by citations

Authors
Savage, H., Pareek, S., Lee, J., Ballarò, R., Conterno Minussi, D., Hayek, K., Sadullozoda, M., Lochmann, B. S., McQuade, J. L., LaVoy, E. C., Marmonti, E., Patel, H., Wang, G., Imanishi, M., Kotla, S., Abe, J.-I., & Schadler, K.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • 2Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center UTHealth, Houston, Texas.
  • McGill University (CA)
  • University of Houston (US)
  • Houston Methodist (US)
Corresponding author
Schadler, Keri
Venue
Cancer Immunology Research
Published
2023-06-12
Volume
11
Issue
9
Pages
1168-1183
ISSN
  • 2326-6066 (ISSN-L)
  • 2326-6074
OpenAlex
W4380357935
Cited by
30
References
40
Citations by year
2026: 10 · 2025: 9 · 2024: 9 · 2023: 2
FWCI
3.64
Type
journal article
Language
en
Open access
Locations
  • Cancer Immunology Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
Funders
  • Cancer Prevention and Research Institute of Texas (RP190256)
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute (5P50CA221703-04)
  • NHLBI Division of Intramural Research (CA016672, AI-156921)
  • National Cancer Institute (P30CA016672, CA016672)
  • Schissler Fellowship
  • Pauline Altman-Goldstein Foundation Discovery Fellowship
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
Keywords
aerobic exercise, melanoma, tumor microenvironment, ERK5, tumor vasculature normalization, VCAM-1, tumor-associated macrophages, macrophage polarization, CD8+ T cells, tumor hypoxia, tumor growth, MHC class II
MeSH terms
Animals, Melanoma, Phenotype, Phosphorylation, CD8-Positive T-Lymphocytes, Mitogen-Activated Protein Kinase 7, Mice, Tumor Microenvironment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review