Evidence map›Paper›PMID 42649907›Full record

ReviewCancers2026

Next-Generation Immune Checkpoint Inhibitors in Gastrointestinal Cancers: Mechanisms, Resistance, and Emerging Therapeutic Strategies.

Mariam Ismail, Zaid Alabed, Khaled Alhallaq, Ebtesam Al-Najjar, Nour Mustafa, Yacoub Aldroubi, Yazan Hamdaneh, Abdullah Esmail

Abstract readReview
In one paragraph

Review in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Mariam IsmailFaculty of Medicine, Delta University for Science and Technology, Gamasa 11152, Egypt.
Zaid AlabedFaculty of Medicine, The University of Jordan, Amman 11942, Jordan.
Khaled AlhallaqFaculty of Medicine, The University of Jordan, Amman 11942, Jordan.
Ebtesam Al-NajjarDepartment of Medicine, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA.
Nour MustafaFaculty of Medicine, The University of Jordan, Amman 11942, Jordan.
Yacoub AldroubiFaculty of Medicine, The University of Jordan, Amman 11942, Jordan.
Yazan HamdanehDepartment of Medicine, Methodist Healthcare System of San Antonio, TX 78229, USA.
Abdullah EsmailDepartment of Medicine, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX 77030, USA.ORCID 0000-0002-2337-8351

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immune checkpoint inhibitors (ICIs) have significantly changed the treatment landscape of several gastrointestinal (GI) malignancies, particularly microsatellite instability-high (MSI-H) and mismatch repair-deficient (dMMR) tumors. However, most GI cancers remain resistant to current PD-1/PD-L1-based immunotherapy because of complex and highly suppressive tumor microenvironments characterized by immune stromal exclusion, myeloid-driven immune suppression, defective antigen presentation, and adaptive immune resistance mechanisms. Emerging evidence suggests that alternative inhibitory pathways, including lymphocyte activation gene-3 (LAG-3), T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and V-domain Ig suppressor of T-cell activation (VISTA), contribute substantially to persistent T-cell dysfunction and resistance to checkpoint blockade. This review summarizes the immune landscape of GI malignancies and discusses the biological mechanisms underlying resistance to current ICIs. We highlight the evolving role of next-generation immune checkpoints, ongoing clinical development of novel inhibitors, and emerging combination strategies involving chemotherapy, anti-angiogenic therapy, radiation, bispecific antibodies, and tumor microenvironment modulation. In addition, we discuss current limitations in biomarker development and the growing role of circulating tumor DNA, spatial immune profiling, and multi-omics approaches in patient selection. Finally, we explore future directions aimed at improving precision immunotherapy and expanding durable responses across GI cancers.

Indexed as

ctDNAGI oncologyICIsimmune checkpoint inhibitorsTIGIT

Identifiers

PMID42649907
PMCPMC13511401

What Socratic holds

Textmetadata
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.