We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy. We systematically searched three databases (PubMed, Web of Science and Embase) up to 20 February 2023. Extracting the effect size and 95% confidence intervals for overall survival (OS), progression-free survival (PFS) and the objective response rate (ORR). A total of 65 articles were included. We identified the following factors that benefit ICI therapy: smoking status (PFS: 0.72 [0.62, 0.84], p < .001), chemotherapy (PFS: 0.68 [0.58, 0.79], p < .001), expression of programmed cell death ligand 1(PD-L1) (≥1%, ≥5%, or ≥10%) (≥1%: 0.76 [0.71,0.82], p < .001; ≥5%: 0.62 [0.52, 0.74], p < .001; ≥10%: 0.42 [0.30, 0.59], p < .001). We also identified three adverse factors: epidermal growth factor receptor mutations (OS: 1.57 [1.06, 2.32], p = .02), with liver metastases (OS: 1.16 [1.02,1.32], p = .02) and antibiotics (OS: 3.13 [1.25,7.84], p < .001; PFS: 2.54 [1.38, 4.68], p = .003). The results of this umbrella meta-analysis first supported pre-existing understandings of the relationship between beneficial and adverse factors with the efficacy of ICI therapy. In addition, the overexpression of PD-L1 may adversely affect patients.

Background: The utilization of neoadjuvant therapy is progressively expanding in various clinical settings. However, the absence of a clinically validated biomarker to evaluate the treatment response remains a significant challenge in the field. Circulating tumor DNA (ctDNA) detection, a novel and emerging monitoring approach in the field of oncology, holds promise as a potential prognostic biomarker for patients with cancer. This meta‐analysis investigated the clinical significance of ctDNA detection as a predictive tool for cancer recurrence in patients receiving neoadjuvant treatment.Methods: A comprehensive systematic literature search was conducted using public databases to identify relevant studies that investigated the association between ctDNA detection and cancer recurrence in patients receiving neoadjuvant treatment. Hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CI) were calculated to assess the relationship between cancer recurrence and relevant factors. Cancer recurrence was considered the primary outcome.Results: A total of 23 studies encompassing 1590 patients across eight different cancer types were included in the final analysis. Positive ctDNA detection was significantly associated with higher cancer recurrence, especially at post‐neoadjuvant treatment and post‐surgery time points. The risk values for the different cancer categories and geographic areas also differed significantly.Conclusion: Our comprehensive meta‐analysis revealed a significant positive correlation between ctDNA detection and a higher risk of cancer recurrence in patients receiving neoadjuvant treatment. In addition, the risk of recurrence was influenced by variations in cancer type, timing of detection, and geographic region. These findings highlight the promising clinical applicability of ctDNA as a prognostic marker and monitoring approach for patients with cancer. However, the precise mechanism is unknown and more evidence is needed for further research.

Background/Objectives: L1 cell adhesion molecule (L1CAM) has been implicated in colorectal cancer progression, but its cellular source and immune microenvironmental context remain incompletely defined. This study aimed to characterize the expression pattern, cellular localization and immune-associated features of L1CAM in colorectal cancer using public bulk and single-cell datasets. Methods: TCGA, GTEx and CPTAC/UALCAN datasets were used to assess L1CAM expression, protein abundance and clinical associations across cancers, with a focus on colorectal cancer. Single-cell RNA sequencing data from GSE178341 were analyzed to identify L1CAM-expressing cell populations, characterize transcriptional programs and evaluate sample-level associations with immune-cell composition and T/NK cytotoxicity signatures. Candidate ligand-receptor interactions and conceptual mod el-based sensitivity analyses were used to explore stromal-immune communication axes. Supplementary external single-cell datasets were analyzed exploratorily. Results: In colorectal cancer, L1CAM showed tumor-normal expression differences and was associated with progression-free interval, but not overall survival. Single-cell analysis detected L1CAM mainly in rare fibroblast and epithelial subsets rather than T/NK cells. L1CAM-positive fibroblasts showed neural-like, wound-response and matrix-remodeling transcriptional features. In the main cohort, L1CAM-Fib+ samples showed lower T/NK cytotoxicity transcriptional signatures, whereas supplementary external datasets did not reproduce the same direction of association. Candidate communication analyses nominated Galectin, HLA-E, TGFB and extracellular matrix-related axes. Conclusions: These findings suggest that L1CAM-positive fibroblast-associated stromal states provide a dataset-specific exploratory context for interpreting L1CAM-associated immune features in colorectal cancer. The results should be considered hypothesis-generating and require spatial and functional validation.