November 22, 2022

Role of Bacteria in Cancer Growth | RNA-seq

In cancer patients, the malignant cells in the tumors are surrounded by a network of non-malignant cells that can have tumor-promoting or tumor-inhibiting effects, depending on cell type and abundance. In this context, the tumor-associated microbiota plays an important role. Microbiota refers to the totality of all microorganisms in an area, so by tumor-associated microbiota we mean all microorganisms associated with the tumor. Why is it so important?

Previously published studies suggest that bacteria in the microbiota play a role in cancer development, metastasis, immune surveillance, and in the sensitivity of cancer cells to growth-inhibiting drugs in the context of cancer therapy (chemoresistance). This tumor-associated microbiota is an important component of the tumor environment in at least 33 types of cancer.

The problem: Little do we know about the specific identity of host cells through which tumor-associated microbes interact with the patients’ tumor cells. In terms of identifying specific cells that harbor organisms, there is little evidence, and one struggles to recognize the impact of precise host-microbial cellular interactions and the spatial distribution of the intratumoral microbiota on their functional capabilities within the tumor microenvironment (TME).

To address this research gap, researchers from the Fred Hutchinson Cancer Center in Seattle and other centers studied the spatial, cellular, and molecular host–microbial interactions in oral squamous cell carcinoma (OSCC) and colorectal cancer (CRC). They mapped the interactions within the TME using single cell RNA sequencing (scRNA-seq) and in situ spatial profiling technology.

Techniques used

10x Visium spatial transcriptomics technique allowed them to detect the identity and location of viable bacteria in intact tumor tissue from cancer patients.
Using GeoMx digital spatial profiling, they showed that bacterial communities populate microniches that are less vascularized and highly immunosuppressive compared to bacteria-negative tumor regions.
Using a custom-developed single-cell RNA sequencing method they call INVADEseq (invasion-adhesion-directed expression sequencing), they were able to identify cell-associated bacteria and the host cells with which they interact.

To investigate bacterial–host cell-to-cell interaction within the TME and the effect on host cell transcriptomics, we developed INVADEseq (invasion–adhesion-directed expression sequencing) by introducing a primer that targets a conserved region of bacterial 16S rRNA, facilitating the generation of cDNA libraries with bacterial transcripts from the bacteria-associated human cells.
Niño et al., 2022

Findings

The authors conclude that the intratumoral microbiota is heterogeneously distributed across human tumors. Furthermore, it is an important component of the TME that can alter the biology of various cellular compartments and influence anti-tumor immunity and cancer epithelial cell migration: the presence of bacteria in a tumor is an organized process in microniches with immune and epithelial cell functions that affect cancer progression.

Although the authors focused on two gastrointestinal cancers, the technologies could be used to analyze the 33 major cancer types in which an intratumoral microbiota has been demonstrated to date.