The tumor microenvironment is increasingly recognized as a complex ecosystem in which the intra-tumoral microbiota (comprising bacteria, fungi, viruses, etc.) plays a pivotal, underappreciated role in cancer biology. This review systematically summarizes the latest research into the origins, diversity, and functional mechanisms of intra-tumoral microbiota, emphasizing their dual roles in tumor formation, progression, and response to treatment. Using high-throughput sequencing, spatial multi-omics, and integrative bioinformatics, we identify the multifactorial origins of tumor-resident microbiota, including translocation from adjacent tissues, hematogenous dissemination, and viral genomic integration. We also examine the significant inter- and intra-tumoral microbial heterogeneity influenced by anatomical, environmental, and immunological factors, and the tissue-specific functional effects of important microbial species. We detail the mechanisms by which the intra-tumoral microbiota modulate innate and adaptive immunity through pattern recognition receptor signaling, microbial antigen presentation, and microbial metabolite production, ultimately influencing tumor microenvironment composition, immune cell dynamics, and therapeutic efficacy. Finally, we critically evaluate emerging microbiota-targeted therapeutic strategies, including engineered bacteria, antibiotics, bacteriophages, and oncolytic viruses, while outlining the technical, mechanistic, and regulatory challenges that hinder their clinical translation. Our synthesis highlights the need for rigorous multi-omics profiling, causal inference, and smart delivery systems to exploit the intra-tumoral microbiota for precision oncology. This paradigm shift offers unprecedented opportunities for personalized diagnosis and therapy, marking a new frontier in cancer research and treatment.

The CKLF-like MARVEL transmembrane domain containing (CMTM) family of genes comprises CKLF and CMTM1–8 (previously called chemokine-like factor superfamily 1–8, CKLFSF1–8). The CMTM family proteins contain a structurally conserved MAL and related proteins for vesicle trafficking and membrane linking (MARVEL) domain. Dysregulated expression of multiple CMTM family members is a common feature in many human cancer types. CMTM proteins control critical biological processes in cancer development, including growth factor receptor activation and recycling, cell proliferation, apoptosis, metastasis, and immune evasion. Emerging in vivo and in vitro evidence indicates that the mechanisms of action of most CMTM proteins are complex and multifactorial. This review highlights new findings regarding the roles of CMTM1–8 in cancer, particularly in tumor growth, metastasis, and immune evasion. Additionally, the potential clinical value of CMTMs as novel drug targets or biomarkers is discussed.