In colorectal cancer (CRC), whether the immune score can be used to predict the clinical prognosis of the patient has not been completely established. Besides, the prognostic values of tumor-infiltrating lymphocytes (TILs) in different anatomical locations, counting sites, and subtypes have been controversial. The purpose of this meta-analysis is to analyze and determine the prognostic value of TILs indices including TIL subsets, infiltrating sites, and anatomical sites. Relevant literature was obtained by searching PubMed and Google Scholar. The pooled hazard ratio (HR) of the overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) was computed to investigate the prognostic significance of CD3+, CD8+, CD45RO+, and FOXP3+ T cells. A total of 22 studies involving 5108 patients were included in the meta-analysis. In CC, based on T cell subtypes analysis, the final results indicated that CD8+ and FOXP3+ infiltrating cells, but not CD3+ T cells were prognostic markers for DFS and OS. In addition, with regard to the counting location of TILs, subgroup analysis revealed that only high FOXP3+ infiltrates in the tumor stroma (ST) were significantly associated with OS (HR = 0.38, 95% confidence interval (CI) = 0.22–0.67, P = 0.0007), whereas in invasive margin (IM), high density of CD3+ infiltrating cells indicated increased DFS (HR = 0.76, 95% CI = 0.62–0.93, P = 0.008). At the tumor center (TC), high CD8+ T cells infiltration was associated with improved DFS (HR = 0.50, 95% CI = 0.38–0.65, P < 0.00001). In RC, whether CSS or OS, high-density TIL was associated with improved prognosis. In a single counting site, high-density TILs reflect favorable prognostic value in CC or RC. For CC, more prospective studies are needed to verify whether different anatomical sites affect the distribution of TILs and thus the prognosis of patients. For RC, further studies should analyze the prognostic value of the immune score.

Cancer microenvironment is composed of numerous components that can support cancer cell proliferation, promote cancer progression and contribute to cancer treatment resistance. The major components of caner microenvironment are fibroblasts, endothelial cells, immune cells as well as cytokines, chemokines, and extracellular matrix (ECM) all of which surround tumor cells as the core and cross talk with each other. Among them, cancer-associated fibroblasts (CAFs) play an important role in promoting cancer progression by secreting various pro-inflammatory factors. MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate protein expression both in cancer cell and normal stromal cells. Changes of miRNAs expression in cancer-associated fibroblasts can be induced both by cancer cells and other stromal cells. This change can arise through direct interaction or by secreted paracrine factors or even by secreted miRNAs. The desregulated miRNAs in cancer-associated fibroblasts then enhance the CAFs phenotype and assist their cancer promotion ability. Explore the regulatory function of miRNAs in the complex communication between cancer cells and cancer microenvironment is important to understand the process of tumor progression and may help to develop new therapeutic strategies. This review provides an updated content of latest research advances about the relevance of miRNAs in the interaction between cancer cells and the CAFs. We will describe miRNAs which are differential expressed by NFs and CAFs, their function in regulating fibroblasts activation as well as miRNAs expressed in CAFs as prognostic factors in cancer stroma in recent studies. We will also discuss miRNA as an important player in CAFs mediated regulation of cancer progression and metastasis, cancer metabolism, cancer stem cell property and chemoresistance.

Tumor-associated regulatory T cells (Tregs) are important effectors in the tumor microenvironment (TME), acting as accomplices in the promotion of tumor progression. Currently, the importance of removing the immunosuppressive activity in the TME has received its due attention, and Tregs have been focused on. The cytokine-receptor axes are among the essential signaling pathways in immunocytes, and tumor-associated Tregs are no exception. Therefore, manipulating cytokine-receptor pathways may be a promising effective strategy for treating various malignancies. Here, we summarize the classification, immunosuppressive mechanisms, existing immunotherapies, and potential biomarkers related to tumor-infiltrating Tregs to guide the development of effective cancer immunotherapies.

Immunoscore can accurately predict the prognosis of patients with stage I–III colorectal cancer. However, whether it can be used to predict the prognosis of colorectal cancer peritoneal metastases (CRCPM) remains to be validated. We analyzed peritoneal and ovarian metastases in 68 patients with CRCPM. The immunoscore (IS) was based on the infiltration level of CD3+ and CD8+ T cells, whereas the TBM score was derived from the infiltration level of CD3+, CD8+, CD20+ and CD163+ cells to tumor microenvironment (TME). The predictive value of IS and TBM scores for relapse-free survival (RFS) and overall survival (OS) of patients with CRCPM was analyzed using Kaplan Meier curve and Cox multivariate models. Significant difference in the infiltration levels of different immune cell subtypes in primary lesions, peritoneal metastasis and ovarian metastasis were compared using t-test.CRCPM patients with high IS (>1), high TBM1 score (≥2) or high TBM2 score (≥2) had a significantly longer OS (IS: median OS, not reached vs 23 months, p = .0078; TBM1: not reached vs 21.5 months, p = .013; TBM2: 39.3 months vs 15.2 months, p = .001). On the other hand, patients with high IS had a trend of improved RFS (13.4 months vs 11.0 months, p = .067). However, TBM1 and TBM2 score has no predictive utility for RFS. Multivariate analysis revealed that IS, TBM1 and TBM2 can accurately predict OS, but not RFS. Finally, the infiltration level of CD3+ T cells, CD8+ T cells, CD20+ B cells, and CD68+ macrophage was significantly higher in peritoneal metastatic tissue and ovarian metastatic tissue, relative to primary tumor tissues.The IS and TBM score of peritoneal metastases could effectively predict OS of patients with CRCPM. Peritoneal metastasis of colorectal cancer decreased the infiltration level of T and B cells.

Reports indicate that most metastatic ovarian cancer (MOC) originates from gastrointestinal cancer (GIC). Notably, GICs metastasize to the ovary frequently via 3 main routes including hematogenous spread, lymphogenous spread, and transcoelomic spread. Nonetheless, the mechanism of the progression remains unknown, and only a handful of literature exists on the molecular alteration implicated in MOC from GIC. This work collected existing evidence and literature on the vital molecules of the metastatic pathway and systematically analyzed them geared toward exploring the mechanism of the metastatic pathway of MOC. Further, this review described dominating molecular alteration in the metastatic process from cancer cells detaching away from lesions to arrive at the ovary, including factors for regulating signaling pathways in epithelial-interstitial transformation, invading, and surviving in the circulatory system or abdominal cavity. We interrogated the basis of the ovary as a distant metastatic site. This article provides new insights into the metastatic pathway and generates novel therapeutic targets for effective treatment and satisfactory outcomes in GIC patients.