Evidence mapPaperPMID 41584608Full record

ReviewFrontiers in oncology2025

Pharmacological strategies to overcome immune checkpoint inhibitor resistance in non-small cell lung cancer.

Yuyu Xu, Huiling Shen, Dong Shang, Cailin Zhu

Abstract readReview
In one paragraph

Review in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

4 authors.

Yuyu XuDepartment of Oncology, Zhenjiang First People's Hospital, Zhenjiang, China.
Huiling ShenDepartment of Oncology, Zhenjiang First People's Hospital, Zhenjiang, China.
Dong ShangDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Cailin ZhuDepartment of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immune checkpoint inhibitors (ICIs) have redefined the therapeutic paradigm of non-small cell lung cancer (NSCLC), offering durable remission in select patients by reactivating anti-tumor T cell responses. Yet, this clinical triumph is tempered by the reality that most patients experience either primary resistance or relapse due to acquired resistance, underscoring an urgent need for mechanistically grounded solutions. Resistance arises through a complex interplay of tumor-intrinsic mechanisms, including defects in antigen presentation, interferon signaling disruption, and oncogenic pathway activation (EGFR, KRAS, MET), and tumor-extrinsic factors such as immunosuppressive cell populations, inhibitory cytokines, and metabolic rewiring of the tumor microenvironment (TME). This review provides a comprehensive synthesis of emerging pharmacological strategies aimed at reversing ICI resistance in NSCLC. Promising avenues include dual or multi-checkpoint inhibition (targeting LAG-3, TIGIT, TIM-3), integration of epigenetic reprogrammers to resensitize immune-silent tumors, and metabolic interventions that normalize the TME. Additionally, combination regimens with oncogene-directed therapies, engineered cytokine analogs, neoantigen-based vaccines, and adoptive T cell therapies are reshaping the frontier of immunoresistant NSCLC management. We also highlight pivotal clinical trials-both completed and ongoing that illuminate translational breakthroughs and therapeutic pitfalls. Looking ahead, the field must grapple with key challenges: the refinement of predictive biomarkers, stratification of patients through genomic, immunologic, and microbiome-based profiling, and the management of toxicity in complex combination protocols. Ultimately, a shift toward highly personalized, biomarker-guided therapeutic strategies holds the greatest promise for overcoming resistance and extending the reach of immunotherapy in NSCLC.

Indexed as

epigenetic modulationimmune checkpoint inhibitors (ICIs)immunotherapy resistancenon-small cell lung cancer (NSCLC)PD-1/PD-L1 blockadetumor microenvironment (TME)

Identifiers

PMID41584608
PMCPMC12824025

What Socratic 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 Socratic graph.