Association of Intratumoral Microbiota With Prognosis in Patients With Nasopharyngeal Carcinoma From 2 Hospitals in China

Abstract

Key Points Question Is there characteristic microbiota in nasopharyngeal carcinoma (NPC) tissues and, if so, is it associated with prognosis? Findings In this multicenter cohort study including 802 patients with NPC, we confirmed the existence of microbiota within NPC tissues, which mainly originated from the nasopharynx. Intratumoral bacterial load was associated with poor survival in patients with NPC and was negatively associated with T-lymphocyte infiltration. Meaning The results suggest that the intratumoral bacterial load may be a reliable prognostic indicator for patients with NPC.

Tumour microbiota structure predicts hypopharyngeal carcinoma recurrence and metastasis

“…In recent years, increasing researches have confirmed the presence of intratumor microbiota, providing biological basis of the application of intratumor microbiota as a promising prognostic biomarker [ 27 ]. Microbiome studies of multiple tumours have demonstrated the microbiota-associated oncological outcomes [ 14 , 28 ]. Although the exact mechanism has not been fully elucidated, tumour microbiota may affect oncological outcomes via (1) enhancing tumour progression and metastasis; (2) educating local immunity response; (3) influencing anti-tumour therapy ( Figure 6 ).…”

Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy

“… 248 Qiao et al conducted a retrospective cohort study of biopsy specimens from 802 patients with nasopharyngeal carcinoma in two hospitals of China, and found that the intratumoral microorganisms were mainly Corynebacterium and Staphylococcus , which could be used as prognostic tools, and the high bacterial load was negatively correlated with disease-free survival, survival without distant metastasis, overall survival and T cell infiltration. 249 High levels of F. nucleatum in esophageal squamous cell carcinoma showed poor response to neoadjuvant chemotherapy and predicted worse recurrence-free survival. 245 However, in patients with stage II/III non-MSI-high/non-sigmoid colorectal cancer receiving oxaliplatin-based adjuvant therapy, intratumoral F. nucleatum is an independently good prognostic factor.…”

“…104 Moreover, F. nucleatum levels were inversely associated with CD3 + T cell density in breast cancer tissues, 105 and the analysis of transcriptome and digital pathology also showed that intratumoral bacterial load was negatively correlated with T cell infiltration. 106 Intratumoral Methylobacterium could induce the dysfunction of CD8 + tissueresident memory cells in the tumor microenvironment of gastric cancer and promote tumor progression. 107 Immunosuppression.…”

Potential links between the microbiota and T cell immunity determine the tumor cell fate

“…It has been determined that microorganisms also reside in sites outside of the gut and other portals of entry [ 52 , 55 , 56 ], particularly in tumors, where they represent underappreciated environmental agents and can exert regulatory functions on the TME immune and inflammatory program [ 44 ]. Up to now, a tumor microbiome has been characterized in many tumor types, such as pancreas cancer [ 49 , 57 ], prostate cancer [ 58 ], breast cancer [ 59 ], melanoma [ 60 ], gastric cancer [ 61 ], thyroid cancer [ 62 , 63 ], renal cell carcinoma (RCC) [ 64 ], nasopharyngeal carcinoma (NPC) [ 65 ], lung cancer [ 66 , 67 ], and cutaneous T cell lymphoma (CTCL) [ 68 , 69 ] (Table 1 ); Nevertheless, because of its low biomass, the characterization of the intratumor bacterial colonies has remained challenging. More recently, comprehensive analysis of more than 1500 tumor microbiomes across seven cancer types, using a mixture of assays like next-generation sequencing coupled with immunohistochemistry (IHC) and RNA fluorescence in situ hybridization (FISH), showed that (i) in many human solid tumors, LPS and bacterial RNA and DNA can be detected; (ii) intratumor bacteria are mostly intracellular and are present in both cancer and immune cells; (iii) a more diverse and richer microbiome than seen in other tumors is found in breast tumors, including live bacteria from three main phyla Firmicutes , Actinobacteria , and Proteobacteria ; (iv) distinct microbial compositions are present in different tumor types, whereby the microbiome of pancreatic cancer is dominated by Proteobacteria ; Fusobacterium nucleatum was also reported as a dominant bacterial species in pancreatic and breast tumors; the most represented taxa in non-gastrointestinal tumors were species from the Actinobacteria phylum such as Micrococcaceae and Corynebacteriaceae families; and the most abundant bacteria in colorectal tumors belong to the Bacteroidetes and Firmicutes phyla [ 70 ].…”