In a recent paper released in the journal Immunity in which the authors discussed the results of the study of 2022 that was conducted by Galeano Nino et al., which reported that tumor-associated microbiota form micro-niches that contribute to epithelial and immune mediators for cancer.
An increasing body of evidence suggests that microbiomes play an important role in the development of health and illness. While cancers are thought to be as being genetically-based, studies indicate that microbial connections are a key factor in the microenvironment that surrounds cancerous cells and in the spread and growth of cancers. But, the molecular mechanisms of the microbiota’s role in regulating the tumor’s microenvironments and their function in the response to immunotherapies and other cancer treatments remain elusive.
The advent of sequence-based analyses as well as computational instruments, in conjunction with traditional microscopy and flow cytometry techniques, offer the opportunity to investigate the interactions between host cells and microbial species in different types of cancer. Studies have shown that the diversity of microbiomes differs with the different types of cancer and the microorganisms that are associated with particular tumors and their role in the tumor’s microenvironment was not known. Galeano Nino et al. employed single-cell ribonucleic acids sequencing (scRNA-seq) as well as bulk sequencing as well as spatial imaging to deal with these issues.
The most important discoveries
The study of Galeano Nino and co. discovered that microbiomes are distributed within specific compartments of the cell that may be linked to specific roles in the development of tumors. The analysis of 16S RNA sequences from tissues from 11 patients with colorectal cancer discovered that tumors have diverse associations with microorganisms and colon cancers and also had an established connection to Fusobacterium nucleatum.
In addition, the use of a spatial transcriptomics platform was utilized to study the distribution and identity of microbiota from the intratumoral region in oral and colorectal cancers involving squamous cells. Microbiological ribosomal RNA (rRNA) transcripts were typically discarded when analyzing human scRNA-seq datasets and were utilized to measure the transcriptional load of each microorganism. This technique was able to identify transcriptional transcripts of bacterial cells in 46 percent and 28% of oral Squamous cell carcinoma tumor-capturing locations as well as oral squamous cell carcinoma tumor-capture locations, respectively. The results indicated a unidirectional association of microbiota in niches within the tumors.
Furthermore, 77 cancer progression and anti-tumor immune-related proteins were employed as a proteomic method to study the microbiota’s spatial distribution within tumors. To conduct this analysis, researchers chose epithelial and immune tumor compartments. The bacteria that resided in these immune spaces were detected in micro-niches that are immunosuppressive and have lower levels of T cells as well as maturing myeloid cells. This suggests that tumor regions that contain bacteria hinder the function and recruitment of T cells and recruit the myeloid population.
Comparatively to areas that did not have bacteria, regions with bacteria that were positive within the epithelial layer had lower levels of the tumor-specific protein, p53 as well as lesser vascularization, in addition to an increase in mitogen-activated protein kinase signals and reduced proliferative capacity. Contrary to what was previously known about angiogenesis in tumors These results suggested an increase in the number of blood vessels.
Galeano Nino et al. also developed a method called invasion-adhesion-directed expression sequencing or INVADEseq to determine associations between bacterial and specific host cell types. This technique allows 16S rRNAs of bacteria and human RNAs from the same cells to be sequenced simultaneously which can be useful in identifying microorganisms linked with specific cancer cells. INVADEseq was employed to detect cancerous cells and to analyze the bacterial and human transcriptomes of three cancerous colorectal cell lines as well as seven oral squamous cell cancer patients.
The INVADEseq technology can also be used to assess transcriptomes of the same type of cancer with bacteria and without. The results indicated that microbe-infected cells were more likely to express signaling pathways that are associated with metastasis, deoxyribonucleic acids (DNA) repair, and cancer cell invasion and dormancy.
Furthermore, the culturing of colorectal cancer spheroids that had and without colorectal tumors of F. nucleatum revealed that when embedded in neutrophil-containing collagen matrices, the neutrophils formed clusters within the spheroids when F. nucleatum was present. However, when there were no microorganisms, the neutrophils moved around freely. In conjunction with the finding that bacteria-positive niches attract myeloid cells, these findings indicate that the microbiomes that are connected to tumors can increase cancer cells’ capacity to spread.
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In the end, the results of the study conducted by Galeano Nino and co. revealed that tumors have particular microbial immunosuppressive niches which increase myeloid cell numbers and decrease T-cell function. These findings suggest that microbiomes could play various roles throughout the process of neoplastic. In addition, the niches of microbial life connected with the migration of myeloid cells may be therapeutic targets for the treatment of cancer.