ReviewOncoTargets and therapy2026
Mechanisms and Emerging Strategies to Overcome Immunotherapy Resistance in Cold Tumours of Colorectal Cancer.
Review in OncoTargets and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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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.
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0 citing papers in PubMed.
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapy in colorectal cancer (CRC) presents a striking dichotomy. MSS/pMMR tumors account for approximately 95% of metastatic CRC cases, representing a substantial global health burden. While immune checkpoint inhibitors (ICIs) have revolutionized treatment for mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic CRC-achieving durable responses in tumors with high mutational burden and a T-cell-inflamed microenvironment-the majority of microsatellite stable (MSS) cases remain resistant. The MSS tumor microenvironment is typically "cold", featuring low neoantigen load, poor T-cell infiltration, and dominant immunosuppressive networks. To overcome this resistance, extensive research is focused on combination strategies (ICIs with anti-angiogenic agents, targeted therapies, chemotherapy, radiotherapy) and next-generation modalities (adoptive cell therapies, bispecific antibodies, cancer vaccines). This review examines the biological basis for this dichotomy, summarizes clinical evidence in dMMR/MSI-H CRC, and critically assesses emerging strategies for MSS disease. We propose that future progress will likely depend on mechanism-based, biomarker-driven approaches that match specific immune evasion patterns with rationally designed interventions, with the goal of extending immunotherapy benefits to broader CRC populations. This narrative review synthesizes peer-reviewed literature from PubMed and clinical trial registries (2015-2025), prioritizing Phase II/III trials and mechanistic studies.
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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.