The role of Gram-positive cocci in cancer initiation, progression, and its application in therapy

Tumors are one of the most critical health issues and a leading cause of human mortality. Over the past two decades, research on the human microbiome and its functions has revealed microbiota-focused strategies for health and disease. Several studies have demonstrated the presence of intratumoral bacteria in many solid tumors, with distinct microbial compositions across different cancer types. Notably, recent studies have shown that the distribution of Gram-positive cocci differs between tumor patients and healthy individuals. Mechanistic investigations indicate that Gram-positive cocci and their metabolites play roles in inducing genomic instability and mutations, influencing epigenetic modifications, promoting inflammatory responses, regulating host immunity, and activating invasion and metastasis. With the deepening understanding of the mechanisms underlying Gram-positive cocci in tumors, novel anti-tumor therapies have been investigated. In this review, we summarize the distribution of Gram-positive cocci within the human body, explore their complex roles in the initiation, progression, and metastasis of tumors, and overview their potential in early cancer diagnosis, prognostic assessment, and therapeutic strategies. Finally, we discuss the prospects and limitations of targeting or harnessing Gram-positive cocci in cancer.