Recent advancements in technology have significantly expanded the scope of tumor research, progressing from the study of individual cells to more intricate tissue and organ-level analyses. Tumor organoids have emerged as a highly realistic platform for investigating tumor growth, development, and their interactions with the surrounding microenvironment. However, a notable limitation of these organoids is their lack of the diverse cellular composition typically observed in actual tumors, which hinders their ability to fully replicate the complexity of the tumor microenvironment. Immune cells play a pivotal role, and tumor immunology has become a major research hotspot. Research in tumor immunology aims to elucidate how the immune system recognizes and attacks tumor cells, as well as how tumor cells evade immune surveillance. In recent years, there has been growing interest in co-culturing immune cells with tumor organoids, an approach that has yielded valuable insights into the intricate interactions between tumors and the immune system. The aim of this paper is to review and discuss the progress achieved in co-culturing tumor organoids with immune cells. By doing so, we hope to offer a new perspective and enhance our understanding of the complexity and diversity inherent in the tumor microenvironment.

Cancer heterogeneity has posed a great challenge to traditional cancer treatment, with the reappearance of cancer heterogeneity of inter and intra patients being especially critical. Based on this, personalized therapy has emerged as significant research focus in recent and even future years. Cancer-related therapeutic models are developing, including cell lines, patient-derived xenografts, organoids, etc. Organoids are three-dimensional in vitro models emerged in the past dozen years and are able to reproduce the cellular and molecular composition of the original tumor. These advantages demonstrate the great potential for patient-derived organoids to develop personalized anticancer therapies, including preclinical drug screening and the prediction of patient treatment response. The impact of microenvironment on cancer treatment cannot be underestimated, and the remodeling of microenvironment also allows organoids to interact with other technologies, among which organs-on-chips is a representative one. This review highlights the use of organoids and organs-on-chips as complementary reference tools in treating colorectal cancer from the perspective of clinical efficacy predictability. We also discuss the limitations of both techniques and how they complement each other well.

Alternative splicing (AS) is an important event that contributes to posttranscriptional gene regulation. This process leads to several mature transcript variants with diverse physiological functions. Indeed, disruption of various aspects of this multistep process, such as cis- or trans- factor alteration, promotes the progression of colorectal cancer. Therefore, targeting some specific processes of AS may be an effective therapeutic strategy for treating cancer. Here, we provide an overview of the AS events related to colorectal cancer based on research done in the past 5 years. We focus on the mechanisms and functions of variant products of AS that are relevant to malignant hallmarks, with an emphasis on variants with clinical significance. In addition, novel strategies for exploiting the therapeutic value of AS events are discussed.

Pancreatic cancer (PACA), which is characterized by an immunosuppressive nature, remains one of the deadliest malignancies worldwide. Aberrant DNA methylation (DNAm) reportedly influences tumor immune microenvironment. Here, we evaluated the role of DNA methylation driven genes (MDGs) in PACA through integrative analyses of epigenomic, transcriptomic, genomic and clinicopathological data obtained from TCGA, ICGC, ArrayExpress and GEO databases. Thereafter, we established a four-MDG signature, comprising GPRC5A, SOWAHC, S100A14, and ARNTL2. High signature risk-scores were associated with poor histologic grades and late TNM stages. Survival analyses showed the signature had a significant predictive effect on OS. WGCNA revealed that the signature may be associated with immune system, while high risk-scores might reflect immune dysregulation. Furthermore, GSEA and GSVA revealed significant enrichment of p53 pathway and mismatch repair pathways in high risk-score subgroups. Immune infiltration analysis showed that CD8+ T cells were more abundant in low score subgroups, while M0 macrophages exhibited an opposite trend. Moreover, negative regulatory genes of cancer-immunity cycle (CIC) illustrated that immunosuppressors TGFB1, VEGFA, and CD274 (PDL1) were all positively correlated with risk-scores. Furthermore, the four signature genes were negatively correlated with CD8+ lymphocytes, but positively associated with myeloid derived suppressor cells (MDSC). Conversely, specimens with high risk-scores exhibited heavier tumor mutation burdens (TMB) and might show better responses to some chemotherapy and targeted drugs, which would benefit stratification of PACA patients. On the other hand, we investigated the corresponding proteins of the four MDGs using paraffin-embedded PACA samples collected from patients who underwent radical surgery in our center and found that all these four proteins were elevated in cancerous tissues and might serve as prognostic markers for PACA patients, high expression levels indicated poor prognosis. In conclusion, we successfully established a four-MDG-based prognostic signature for PACA patients. We envisage that this signature will help in evaluation of intratumoral immune texture and enable identification of novel stratification biomarkers for precision therapies.

Background: Some significant differences exist between the outcomes of left‐ and right‐sided colon cancer patients. The presence of nodal metastases is a critical prognostic factor, especially in the absence of distant metastasis. Our research studied the lymph nodes status of left‐ and right‐sided colon cancer patients to determine the influence of this factor on prognosis.Methods: Our data were obtained from the Surveillance, Epidemiology and End Results (SEER) database. We used the chi‐square test to analyze the clinicopathological characteristics. The X‐tile program was adopted to acquire optimal cutoff points of lymph node index. Kaplan–Meier curves were used to analyze prognosis and multivariate Cox regression models were performed to identify the independent factors associated with survival. Nomograms were built to predict the overall survival of patients, Harrell's C‐index and calibration plots were used to validate the nomograms.Results: The study included 189,941 patients with colon cancer without metastasis (left 69,885, right 120,056) between 2004 and 2015. There are more patients with adequate examined lymph nodes in right‐sided. Lymph node status in patients with right colon cancer has a more significant impact on the risk of death. LODDS (C‐index: 0.583; AIC: 6875.4) was used to assess lymph node status. The nomograms showed that lymph node status was the main factor to predict the outcome in right‐sided colon patients.Conclusions: The influence of lymph node status on predicting prognosis is significantly different between patients with left and right colon cancer without metastasis. The tumor site needs to be considered when lymph node status is used to assess the outcome of patients.