It has been spotlighted that the Tumor Microenvironment (TME) is crucial for comprehending cancer progression and therapeutic resistance. Therefore, this comprehensive review elucidates the intricate architecture of the TME, which encompasses tumor cells, immune components, support cells, and a myriad of bioactive molecules. These constituents collectively foster dynamic interactions that underpin tumor growth, metastasis, and nuanced responses to anticancer therapies. Notably, the TME’s role extends beyond mere physical support, serving as a critical mediator in cancer-cell evolution, immune modulation, and treatment outcomes. Innovations targeting the TME, including strategies focused on the vasculature, immune checkpoints, and T-cell therapies, have forged new pathways for clinical intervention. However, the heterogeneity and complexity of the TME present significant challenges, necessitating deeper exploration of its components and their interplay to enhance therapeutic efficacy. This review underscores the imperative for integrated research strategies that amalgamate insights from tumor biology, immunology, and systems biology. Such an approach aims to refine cancer treatments and improve patient prognoses by exploiting the TME’s complexity.

Fusobacterium functions as both commensal and pathogen, linking the oral–gut axis to diverse diseases, including cancer. Evidence shows it modulates microbial balance, promotes dysbiosis, and contributes to carcinogenesis by driving inflammation, proliferation, invasion, and immune evasion. This review integrates ecological, molecular, and clinical insights, highlighting its roles in oral and systemic disease and discussing therapeutic potential, underscoring Fusobacterium’s dualistic nature and implications for microbiome-targeted interventions.

Hepatitis B virus (HBV) infection has been believed as a major cause of hepatocellular carcinoma (HCC) for a long time, however, the evidences of which are mostly from clinical and epidemiological investigations while there is no evidence from animal experiments. Tree shrew (Tupaia) is a small animal closely related to primates evolutionarily, with about 8 years of lifespan. Our previous study proved that tree shrews can be chronically HBV-infected after being inoculated neonatally with HBV. The present study reports the further results from the longer-term observation of these animals. Neonatal tree shrews were inoculated with sera from HBV-infected patient or tree shrew. Their serum samples and liver biopsies were collected periodically for detection of HBV markers as well as for histopathological and immunohistochemical examinations. Group A consisted of six tree shrews with chronic HBV-infection, and group B consisted of nine tree shrews without chronic HBV infection. Periodical examinations on serum and liver biopsies of the animals in group A showed the progress of HBV infection, and two cases of HCC occurred at their late stage of life. The courses of HBV infection and the hepatic histopathological and immunohistochemical changes in the tree shrews were similar to those in humans. In contrast, neither HCC nor obvious hepatitis histopathological change was found among the tree shrews in group B. The course of HBV infection and the features of HCC discovered in tree shrews are similar to those of chronically HBV-infected humans. The tree shrew model might be used to investigate the underlying mechanisms favoring susceptibility for chronic HBV infection and disease progression.

The extensive morbidity of colorectal cancer (CRC) and the inferior prognosis of terminal CRC urgently call for reliable prognostic biomarkers. For this, we identified 704 differentially expressed genes (DEGs) by intersecting three datasets, GSE41328, GSE37364, and GSE15960 from Gene Expression Omnibus database, to maximize the accuracy of the results. Preliminary analysis of the DEGs was then performed using online gene analysis datasets, such as DAVID, UCSC Cancer Genome Browser, CBioPortal, STRING, and UCSC Cancer Genome Browser. Cytoscape was utilized to visualize the protein perception interaction network of DEGs, and the bubble map of GO and KEGG enrichment function was demonstrated using the R package. The Molecular Complex Detection (MCODE), Biological Network Gene Oncology (BiNGO) plug-in in Cytoscape, was applied to further screen the DEGs to obtain 15 seed genes, which were IL1RN, GALNT12, ADH6, SCN7A, CXCL1, FGF18, SOX9, ACACB, PRRX1, MZB1, SLC22A3, CNNM4, LY6E, IFITM2, and GDPD3. Among them, IL1RN, ADH6, SCN7A, ACACB, MZB1, and GDPD3 exhibited statistically significant survival differences, whereas limited studies were conducted in CRC. Based on the enrichment results of the Gene Ontology(GO) and Kyoto Encyclopedia of Genes and genomes (KEGG) as well as documented findings of key genes, we further emphasized the potential of IL1RN and PRRX1 as markers of immune infiltrates in CRC and confirmed our hypothesis by compiling data from the UALCAN, Tumor Immune Estimation Resource, and TISIDB databases for these two genes. The above-mentioned genes might offer a valuable insight into the diagnosis, immunotherapeutic targets, and prognosis of CRC.

Metalloproteinases (MPs) is a large family of proteinases with metal ions in their active centers. According to the different domains metalloproteinases can be divided into a variety of subtypes mainly including Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteases (ADAMs) and ADAMs with Thrombospondin Motifs (ADAMTS). They have various functions such as protein hydrolysis, cell adhesion and remodeling of extracellular matrix. Metalloproteinases expressed in multiple types of cancers and participate in many pathological processes involving tumor genesis and development, invasion and metastasis by regulating signal transduction and tumor microenvironment. In this review, based on the current research progress, we summarized the structure of MPs, their expression and especially immunomodulatory role and mechanisms in cancers. Additionally, a relevant and timely update of recent advances and future directions were provided for the diagnosis and immunotherapy targeting MPs in cancers.