SynthesisMolecules (Basel, Switzerland)2026
Heating the Cold: Overcoming Immunotherapy Resistance in Microsatellite-Stable Colorectal Cancer: A Systematic Review.
Synthesis in Molecules (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) has shown significant heterogeneity regarding its response to immunotherapy. Long-lasting, beneficial effects have been observed in mismatch repair-deficient, microsatellite instability-high (dMMR/MSI-H) tumours, while mismatch repair-proficient, microsatellite stable (pMMR/MSS) tumours have remained resistant. Such differences in results have been studied in this review through the "hot" and "cold" tumour concept. It explains how various biological and microenvironmental factors play a role in immune resistance and T-cell priming and infiltration. Key factors include a low neoantigen load and defects in antigen presentation, which reduce the overall immune recognition of tumour cells. The review also studies certain processes such as Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signalling and what input they have in the prevention of effective antitumour immune responses. Conventional treatments like chemotherapy and radiotherapy have been considered alongside more targeted treatments such as the inhibition of vascular endothelial growth factor (VEGF) signalling and the suppression of myeloid-mediated immune evasion, to convert "cold" MSS tumours into immune-responsive lesions. Methods which aim to modify the tumour microenvironment such as metabolic reprogramming and microbiome modulation have also been covered in this review. Artificial intelligence and nanomedicine are new technologies that could provide improved patient stratification and therapeutic precision, although their clinical application in pMMR/MSS CRC remains under investigation. A systematic literature search of PubMed and PubMed Central (PMC) was conducted from 10 June 2026 to 19 August 2026 using predefined eligibility criteria, with study selection reported according to PRISMA 2020. Because of substantial heterogeneity in study design, therapeutic approach and reported outcomes, the included evidence was synthesized narratively rather than by meta-analysis. A total of 158 studies were included.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.