Evidence map›Paper›PMID 35040434›Full record

ReviewThe Journal of clinical investigation2022

Fighting in a wasteland: deleterious metabolites and antitumor immunity.

McLane J Watson, Greg M Delgoffe

Open access · goldAbstract readReview
In one paragraph

Review in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
4.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 61 citations in OpenAlex.

  1. DRP1 depletion protects NK cells from hypoxia-induced dysfunction.Redox report : communications in free radical research · 2026
    Article
  2. Review
  3. Malic enzyme 1 senses L-lactate to determine tumor heterogeneity.Signal transduction and targeted therapy · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

McLane J WatsonDepartment of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Greg M DelgoffeDepartment of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
University of Pittsburgh · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
WILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Greg M. Delgoffe · 2004 to 2026
$49.6M
Therapuetic Immune Targeting of EphA2 Expressed by Melanoma & Its Tumor-AssociateP50CA121973 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KIRKWOOD, JOHN MUNN · 2008 to 2018
$22.9M
Training in Cellular & Molecular Mechanisms of Tumor RejectionT32CA082084 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Robert J Binder, Dario AA Vignali · 1999 to 2026
$9.2M
Exploring and exploiting metabolic plasticity in regulatory T cellsDP2AI136598 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DELGOFFE, GREG M. · 2017 to 2017
$2.3M
Illuminating metabolic pathways enabled by early T cell activationR21AI135367 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DELGOFFE, GREG M. · 2018 to 2019
$430k
Lactate transporter MCT1 is required for the high suppressive function of tumor infiltrating regulatory T cellsF31AI149971 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATSON, MCLANE · 2020 to 2021
$86k
NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA097190NCI NIH HHS P50 CA121973NCI NIH HHS T32 CA082084NIAID NIH HHS DP2 AI136598NIAID NIH HHS F31 AI149971NIAID NIH HHS R21 AI135367
6 · The paper itself

Abstract

As cancers progress, they produce a local environment that acts to redirect, paralyze, exhaust, or otherwise evade immune detection and destruction. The tumor microenvironment (TME) has long been characterized as a metabolic desert, depleted of essential nutrients such as glucose, oxygen, and amino acids, that starves infiltrating immune cells and renders them dysfunctional. While not incorrect, this perspective is only half the picture. The TME is not a metabolic vacuum, only consuming essential nutrients and never producing by-products. Rather, the by-products of depleted nutrients, "toxic" metabolites in the TME such as lactic acid, kynurenine, ROS, and adenosine, play an important role in shaping immune cell function and cannot be overlooked in cancer immunotherapy. Moreover, while the metabolic landscape is distinct, it is not unique, as these toxic metabolites are encountered in non-tumor tissues, where they evolutionarily shape immune cells and their response. In this Review, we discuss how depletion of essential nutrients and production of toxic metabolites shape the immune response within the TME and how toxic metabolites can be targeted to improve current cancer immunotherapies.

Indexed as

AdenosineAnimalsHumansImmunotherapyKynurenineLactic AcidNeoplasmsReactive Oxygen SpeciesTumor MicroenvironmentAdenosineKynurenineLactic AcidReactive Oxygen Species

Identifiers

PMID35040434
PMCPMC8759785
OpenAlexW4205958887

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.