Evidence map›Paper›PMID 41583489›Full record

ReviewFrontiers in immunology2025

Adenosine receptors on the immuno-oncology expressway: TIME, perspectives, and translation.

Biswanath Majumder, Santanu Datta

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Dual blockade of adenosine AFrontiers in immunology · 2026
    Article
  3. Review
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.

Biswanath MajumderBugworks Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, Bangalore, India.
Santanu DattaBugworks Research India Pvt. Ltd., Centre for Cellular & Molecular Platforms, National Centre for Biological Sciences, Bangalore, India.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A decade since immune checkpoint inhibitors made a stride in the clinical landscape of oncology, there has been a substantial focus on understanding the response heterogeneity following these therapies. Insights gained from clinical data identified the primary and secondary resistance mechanisms that escape the upfront therapy pressure. Beyond PD-1 and CTLA-4, new checkpoints averting this pressure are under clinical development. Adenosinergic pathways are actively engaged in oncogenic signaling. The main protagonists, CD73, A2AR, and A2BR, span diverse immune subsets of lymphoid and myeloid lineages and have emerged as alternative checkpoints. This review discusses the latest update on immune regulation dynamics of adenosine receptor signaling and their complex interplay with hypoxia in a heterogeneous tumor immune microenvironment (TIME). In this spectrum, we also review the plasticity of A2AR and A2BR in designing new drug candidates, tracing their complex metabolic roots in inducing immune dysfunction. Beyond the existing modalities, the ENT1 and MTAP-loss-MTA axis shows scope for alternative perturbations. The CD39-CD73-A2AR axis plays a central role in the terminal exhaustion of T cells. We highlight the interventions that disrupt the mechanistic context of A2AR and its cooperativity with other suppressors to restore anti-tumor immune functions following inhibition of their multilayered signaling. We capture the ongoing clinical trials and predictive biomarker landscape, along with novel delivery methods, to illustrate the evolving trends in this field. From these perspectives, we discuss how the adenosine axis can widen this new therapeutic avenue and boost the efficacy of CAR-T therapies. Therapeutic cancer vaccines are a new modality in this premise. Finally, an integrated overview of this pathway, along with TIME dynamics, illustrates the barriers and opportunities of combining adenosine signaling inhibitors in clinical trials.

Indexed as

NeoplasmsReceptors, Purinergic P15'-NucleotidaseAnimalsHumansImmune Checkpoint InhibitorsReceptor, Adenosine A2ASignal TransductionT-Cell ExhaustionTumor Microenvironment5'-NucleotidaseImmune Checkpoint InhibitorsReceptor, Adenosine A2AReceptors, Purinergic P1adenosine receptorscancer vaccinesclinical trialsemerging vulnerabilitiesimmune checkpoint resistancesmart deliveryterminal exhaustiontumor immune microenvironment

Identifiers

PMID41583489
PMCPMC12824882

What OpenQuestion holds

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Registered trials

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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.