MSI (Microsatellite instability)

We report an extremely rare case of SR of poorly differentiated CRC with dMMR and marked TILs. Enhanced tumor immunogenicity associated with dMMR and immune activation may contribute to CRC regression.

CTLA-4 expression was detected in 71% of CRCs. CTLA-4 positivity significantly decreased as tumor diameter decreased. There was no significant association between CTLA-4 expression and MSI or other prognostic parameters. Additionally, no significant correlation was found between CTLA-4 expression and median survival time. Nevertheless, the presence of CTLA-4 expression in the majority of CRCs is promising for anti-CTLA-4 therapy.

P1/2, N=358, Recruiting, Xilio Development, Inc. | Trial completion date: Feb 2027 --> Sep 2028 | Trial primary completion date: Feb 2027 --> Sep 2028

P1/2, N=121, Active, not recruiting, Precision Biologics, Inc | Recruiting --> Active, not recruiting | Trial completion date: Jan 2029 --> Nov 2026 | Trial primary completion date: Jan 2028 --> Jun 2026

Microsatellite instability high status (30.77%) and Lynch syndrome (3.85%) can occur in patients with only nonclassic loss of MMR proteins (without the B pattern). It is necessary to deepen our understanding of nonclassical MMR expression patterns to avoid missing patients with microsatellite instability high status and Lynch syndrome.

We further examine key translational barriers, including generalizability, interpretability, and regulatory validation. By integrating multimodal data with mechanistic modeling, AI may help shift CRC immunotherapy from population-level prediction toward dynamic, individualized precision oncology.

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.

Overall, LC-PB-MS/MS enables deep structural lipidomics, uncovering lipid signatures capable of stratifying dMMR/MSI-H CRC patients by therapeutic outcome. The identified lipid markers hold promise for monitoring treatment and for developing novel therapeutic strategies.

Mechanistically, cscR-819 was predominantly localized in the cytoplasm and functioned as a translational regulator, selectively enhancing the translation efficiency of genes involved in cell cycle progression, DNA replication, and antiapoptotic pathways, as demonstrated by polyribosome profiling. In conclusion, our study establishes cscRNAs as functionally relevant contributors to gastric cancer pathogenesis and identifies exploratory associations with tumor immune microenvironment features, positioning cscRNA-based signatures as promising candidate biomarkers for risk stratification and motivating further investigation of cscRNA-immune interactions.

Moreover, PRMT5 blockade diminished M2 macrophage infiltration, inhibited tumor growth, and improved the responsiveness of ELMO1-overexpressing MSI-H CRC to anti-PD-1 immunotherapy. Our findings demonstrate that ELMO1 acts as a novel biomarker to classify the MSI-H group into distinct subtypes and provides a promising therapeutic target for the treatment of ELMO1-overexpressing MSI-H CRC.

Taken together, these findings suggest that OSR2 is associated with prognosis and immune-related features across multiple cancer types. OSR2 may be linked to features of the tumor immune microenvironment through its relationships with immune cell infiltration, immune checkpoint gene expression, and genomic instability, and thus may serve as a candidate biomarker for further investigation in cancer immunotherapy.

P=N/A, N=50, Not yet recruiting, Peking University Cancer Hospital & Institute