# Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression

Source: https://onco.cc/key-papers/paper-chang-cell/  
OnCo record `paper-chang-cell` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one pathway page, indexed on Europe PMC as PubMed record 26321679 and published in Cell; the citing page links this DOI, which is how the record was matched.

## Summary

Failure of T cells to protect against cancer is thought to result from lack of antigen recognition, chronic activation, and/or suppression by other cells. Using a mouse sarcoma model, we show that glucose consumption by tumors metabolically restricts T cells, leading to their dampened mTOR activity, glycolytic capacity, and IFN-γ production, thereby allowing tumor progression. We show that enhancing glycolysis in an antigenic "regressor" tumor is sufficient to override the protective ability of T cells to control tumor growth. We also show that checkpoint blockade antibodies against CTLA-4, PD-1, and PD-L1, which are used clinically, restore glucose in tumor microenvironment, permitting T cell glycolysis and IFN-γ production. Furthermore, we found that blocking PD-L1 directly on tumors dampens glycolysis by inhibiting mTOR activity and decreasing expression of glycolysis enzymes, reflecting a role for PD-L1 in tumor glucose utilization. Our results establish that tumor-imposed metabolic restrictions can mediate T cell hyporesponsiveness during cancer.

Indexed on Europe PMC as PubMed record 26321679 (DOI 10.1016/j.cell.2015.08.016). Matched by DOI alone: one pathway page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Cell
- Year: 2015
- DOI: 10.1016/j.cell.2015.08.016
- Authors: Chang CH, Qiu J, O'Sullivan D, et al.
- What it means: One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Cell 2015: https://doi.org/10.1016/j.cell.2015.08.016
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26321679/
- Europe PMC: https://europepmc.org/article/MED/26321679

## Connected records

- pathways: [Nutrient competition & metabolic immunosuppression](https://onco.cc/pathways/nutrient-competition-tme/)
- journals: [Cell](https://onco.cc/journals/cell/)

---
JSON: https://onco.cc/api/v1/entities/paper-chang-cell.json