Currently, mismatch repair-deficient (dMMR) status is a promising candidate for targeted immune checkpoint inhibition therapy in colorectal cancer (CRC) patients, however, the potential immunological mechanism has not yet been well clarified and some other predictors need to be excavated as well. We collected 330 CRC patients by the match of mismatch repair-proficient (167) and dMMR (163), explored the relationship between MMR status and some important immune molecules including MHC class I, CD3, CD4, CD8, CD56, programmed death-1 and programmed death ligand-1, and investigated the risk factors for dMMR status as well as low MHC class I expression. The Pearson Chi square test was used for analyzing the associations between clinicopathological and immune characteristics and MMR status, and two categories logistic regression model was used for univariate and multivariate analysis to predict the odds ratio of risk factors for dMMR status and low MHC class I expression. Multivariate logistic regression analysis showed that low MHC class I and CD4 expression and high CD8 expression were significant risk factors for dMMR status [odds ratio (OR) = 24.66, 2.94 and 2.97, respectively; all p < 0.05] and dMMR status was the only risk factor for low MHC class I expression (OR = 15.34; p < 0.001). High CD8 and low MHC class I expression suggests the contradiction and complexity of immune microenvironment in dMMR CRC patients. Some other immunocytes such as CD56+ cells might also participate in the process of immune checkpoint inhibition, whereas needs further investigations.

Introduction: This study leverages bioinformatics and medical big data to integrate datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), providing a comprehensive overview of immunogenic cell death (ICD)-related gene expression in colorectal cancer (CRC). The research aims to elucidate the molecular pathways and gene networks associated with ICD in CRC, with a focus on the therapeutic potential of cell death inducers, including ferroptosis agents, and their implications for precision medicine.Methods: We conducted differential expression analysis and utilized advanced bioinformatic techniques to analyze ICD-related gene expression in CRC tissues. Unsupervised consensus clustering was applied to categorize CRC patients into distinct ICD-associated subtypes, followed by an in-depth immune microenvironment analysis and single-cell RNA sequencing to investigate immune responses and cell infiltration patterns. Experimental validation was performed to assess the impact of cell death inducers on ICD gene expression and their interaction with ferroptosis inducers in combination with other clinical drugs.Results: Distinct ICD gene expression profiles were identified in CRC tissues, revealing molecular pathways and intricate gene networks. Unsupervised consensus clustering refined the CRC cohort into unique ICD-associated subtypes, each characterized by distinct clinical and immunological features. Immune microenvironment analysis and single-cell RNA sequencing revealed significant variations in immune responses and cell infiltration patterns across these subtypes. Experimental validation confirmed that cell death inducers directly affect ICD gene expression, highlighting their therapeutic potential. Additionally, combinatorial therapies with ferroptosis inducers and clinical drugs were shown to influence drug sensitivity and resistance in CRC.Discussion: Our findings underscore the importance of ICD-related genes in CRC prognosis and therapeutic targeting. The study provides actionable insights into the efficacy of cell death-inducing therapies, particularly ferroptosis inducers, and their regulatory mechanisms in CRC. These discoveries support the development of precision medicine strategies targeting ICD genes and offer valuable guidance for translating these therapies into clinical practice, with the potential to enhance CRC treatment outcomes and patient survival.

Purpose: To build a new staging system and new prognostic models for MPTB. Methods: We performed a comprehensive analysis of the data from the SEER database. Results: We discussed the characteristics of MPTB by comparing 1085 MPTB cases with 382,718 invasive ductal carcinoma cases. We established a new stage- and age-stratification system for MPTB patients. Furthermore, we built two prognostic models for MPTB patients. The validity of these models was confirmed through multifaceted and multidata verification. Conclusions: Our study provided a staging system and prognostic models for MPTB patients, which can not only help to predict patient outcomes, but also enhance the understanding of the prognostic factors associated with MPTB.

Background: There have not been any head-to-head prospective studies to compare the effects of different chemotherapy regimens as first-line treatments for unresectable pancreatic cancer (UPC). We aimed to compare the effectiveness of nab-paclitaxel plus gemcitabine, mFOLFIRINOX and gemcitabine plus oxaliplatin (GEMOX) as first-line treatments by using real-world data from Chinese patients. Methods: We retrospectively included patients with UPC treated with nab-paclitaxel plus gemcitabine, mFOLFIRINOX or GEMOX as a first-line treatment at Sun Yat-sen University Cancer Center. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed. Results: A total of 117 patients were administered nab-paclitaxel plus gemcitabine (n = 62), mFOLFIRINOX (n = 30) or GEMOX (n = 25) as first-line chemotherapy. The median OS was 11.1, 10.1 and 10.2 months (p = 0.75) in the nab-paclitaxel plus gemcitabine, mFOLFIRINOX and GEMOX, respectively. The ORR was similar among the three groups (24%, 23% and 32%, p = 0.76) and the DCR was higher in the nab-paclitaxel-gemcitabine group (82%) than the other two groups (60% and 64%, p = 0.04). The most common adverse events of grade 3 or 4 were neutropenia (32%, 28% and 5%), peripheral neuropathy (13%, 16% and 0) and fatigue (9%, 16% and 5%). Febrile neutropenia occurred in 2%, 4% and 5% of the patients in the three groups. Conclusion: In the first line treatment of UPC, our results suggest that nab-paclitaxel plus gemcitabine was associated with a higher DCR than mFOLFIRINOX or GEMOX, while all groups demonstrated similar OS, PFS and ORR.

Tumor-infiltrating myeloid cells occupy heterogeneous functional states that are not adequately represented by macrophage abundance or fixed polarization labels. We developed the myeloid damage response index (MDRi), a single-cell-informed framework comprising injury, resolution and antigen-presentation/interferon (APC/IFN) programs, together with a derived injury–resolution axis. MDRi was established in an immune checkpoint blockade-treated multi-cancer atlas containing 47,750 myeloid cells from 192 samples across eight cancer types and assessed separately in an independent multi-cancer myeloid dataset. The programs organized recurrent macrophage and monocyte states along related but non-identical functional dimensions. Non-overlapping antigen-presentation and interferon-response signatures provided gene-independent support for the APC/IFN dimension. Root-sensitivity analyses showed stable state connectivity but root-dependent pseudotime directionality, supporting transcriptional topology rather than a universal developmental sequence. Exploratory response analyses showed concurrent elevation of injury, resolution and APC/IFN scores in post-treatment non-responders, whereas cancer- and regimen-adjusted analyses did not support an independent predictive effect. Complementary T/NK-cell analyses indicated that response-associated immune differences were more evident in pretreatment samples. In primary-tumor TCGA cohorts summarized at the patient level, joint multivariable Cox models containing MDR injury, MDR resolution and MDR APC/IFN identified MDR injury as an adverse factor in selected cancers, whereas resolution and APC/IFN showed cancer- and endpoint-dependent associations. The derived injury–resolution axis was excluded from these joint models because it is mathematically dependent on injury and resolution. Benchmarking against immune-deconvolution and tumor-associated macrophage signatures demonstrated partial but non-uniform overlap. Nasopharyngeal carcinoma Visium and multi-cancer Xenium analyses further revealed platform- and cancer-dependent spatial distributions of MDRi-related programs. MDRi Explorer provides an open-source implementation for scoring, reference comparison and exploratory clinical analysis. MDRi therefore represents a reusable, hypothesis-generating framework for investigating context-dependent myeloid functional organization rather than a universal prognostic signature or clinically validated predictor.

Background: A direct comparison of programmed cell death-(ligand)1 (PD-(L)1) in combination with solvent-based paclitaxel (sb-paclitaxel) or albumin-bound paclitaxel (nab-paclitaxel) in advanced squamous non-small cell lung cancer (NSCLC) is currently lacking. Therefore, we conducted this network meta-analysis (NMA) to compare these two combination regimens. Methods: We systematically searched articles from PubMed, Embase, Cochrane Library, and Web of Science, as well as abstracts from ESMO, ASCO, and WCLC, to identify phase III randomized controlled trials (RCTs) investigating first-line applications of PD-(L)1 inhibitors combined with sb-paclitaxel or nab-paclitaxel in the treatment of advanced squamous NSCLC. Results: The present study consisted of 10 RCTs involving a total of 4352 patients. We compared ICIs+sb-paclitaxel to ICIs+nab-paclitaxel, PD-1+chemotherapy (chem) to PD-L1+chem, and different ICIs combination chemotherapy regimens. Our results revealed that compared to ICIs+nab-paclitaxel, ICIs+sb-paclitaxel exhibited a slightly better OS (hazard ratio (HR): 0.79, 95%CI: 0.58-1.08) and PFS (HR: 0.84, 95%CI: 0.65-1.07), although the differences were not statistically significant. In contrast to PD-L1+chem, PD-1+chem markedly prolonged OS (HR: 0.75, 95%CI: 0.60-0.93) and PFS (HR: 0.79, 95%CI: 0.66-0.96). In terms of the safety profile, there were no differences in the incidence of grade ≥3 TRAEs between ICIs+nab-paclitaxel and ICIs+sb-paclitaxel (RR: 1.05, 95%CI: 0.53-1.99), PD-1+chem and PD-L1+chem (RR: 0.93, 95% CI :0.68-1.28) as well as comparisons among various ICIs+chem regimens. Conclusion: The efficacy and safety of ICIs+sb-paclitaxel is comparable to that of ICIs+nab-paclitaxel in advanced squamous NSCLC. However, ICIs+sb-paclitaxel exhibits a slightly improved PFS, OS, and similar safety profile, making it a potential preferred choice for first-line treatment.