Dietary antigens boost immune T cells and reduce small intestinal cancer

New research has found that common dietary proteins such as bovine serum albumin (BSA) and ovalbumin (OVA) may stimulate the body's immune response and reduce small intestine cancer.

study: Food antigens suppress small intestinal tumorigenesis. Image credit: Sinhyu Photographer / Shutterstock.com

A recent study published in the journal The forefront of immunologyResearchers are investigating the effects of diet antigen For suppression of small intestinal tumors.

How does diet affect small intestine cancer?

Despite gastrointestinal cancer being the most common cancer worldwide, there is still a lack of noninvasive diagnostic techniques to monitor the growth of gastrointestinal (GI) tumors.

Although rare, tumors can develop in the small intestine. Many of these tumors may go undetected for a long time due to delayed onset of symptoms, which may lead to poor treatment outcomes. Therefore, it is of great importance to identify dietary components that prevent or inhibit small intestinal carcinogenesis.

Because small intestine cancer is much rarer than colon cancer, it is unclear which dietary components may suppress the development of small intestine cancer. However, given the important role of the immune system in controlling tumors, researchers hypothesize that food components and bacteria that can affect the immune response in the digestive tract may play a role in the development of small intestine tumors.

About the Research

The researchers of this study^Min/+ Mouse, a mouse model of intestinal tumorigenesis with loss of function mutation In the tumor suppressor gene adenomatous polyposis coli (Apc).

All mice were fed an antigen-free diet (AFD) for 6 weeks in a specific pathogen-free (SPF) environment to study tumors. The AFD incorporated ovalbumin (OVA) or bovine serum albumin (BSA) to examine how the addition of these dietary antigens affected tumor growth and immune responses.

To generate wild-type (WT) mice lacking Peyer's patches (PPs), we injected WT animals with an antibody against interleukin-7 receptor α (IL-7Rα). The offspring of these mice were fed an AFD or a normal diet (NCD) for 5 weeks. At E14.5, WT mothers were translocated to Apc^Min/+ Male mice were injected with the A7R34 antibody to generate Apcs lacking Peyer's patches.^Min/+ animal.

Stereomicroscopy was used to measure tumor size and number, while flow cytometry and fluorescence-activated cell sorting (FACS) allowed the researchers to evaluate immune cell populations. Single-cell ribonucleic acid sequencing (scRNA-seq) was used to investigate immune cell induction in PP in response to dietary antigens.

The researchers were also interested in investigating the involvement of PP in the activation of T cells in the small intestinal lamina propria by food antigens, as this may be the site where food antigens are translocated from the intestinal lumen. To this end, they injected fluorescein isothiocyanate (FITC)-conjugated OVA into ligated small intestinal loops of mice and performed immunohistochemistry (IHC) analysis to confirm this hypothesis.

Microfold (M) cells are a specialized subset of epithelial cells present in the PP that transport large luminal molecules or microorganisms across the plasma membrane. In the current study, we investigated the involvement of M cells in the transport of food antigens to dendritic cells in the PP. In addition to assessing the action of dendritic cells regulated by food antigens that may affect T cell development in the PP, we also measured the abundance of small intestinal lamina propria T cells in M ​​cell-deficient mice.

Research findings

scRNA-seq results revealed that dietary antigens influence the activation of antigen-presenting T cells and dendritic cells. T cells, especially T helper 1 (Th1) cells, in the small intestinal lamina propria prevent the development of cancer in the small intestine.

Mice fed the AFD under SPF and germ-free conditions showed reduced T cell numbers, indicating that dietary antigens contribute to T cell induction and, therefore, to the carcinogenic process. Incorporation of BSA into the diet reduced small intestinal cancer to levels comparable to those of animals fed the NCD. Wild-type mice fed the AFD had reduced cluster of differentiation 4 (CD4)-expressing helper T cells and CD8-expressing cytotoxic T cells in the PP, which were restored after BSA was added to the diet. Addition of OVA to the antigen-free diet restored T cell abundance in the PP, suggesting that this effect is not specific to a particular antigen.

M cells were found to transport dietary antigens from the lumen to dendritic cells, thereby inducing T cell activity. Although dendritic cells were reduced in AFD animals, the addition of BSA to the diet under germ-free and SPF conditions confirmed that dietary antigens modulated dendritic cell function.

Conclusion

Food antigens suppress intestinal carcinogenesis by stimulating T cells in response to food antigens through PP. Cytotoxic T cell activity is an important aspect of the antitumor response. efficacy This depends on the presence of Th1 cells. In the present study, we observed a decrease in the levels of cytotoxic T cells in small intestinal cancer in the AFD-fed APC group.^Min/+ In animals, these levels were partially restored when BSA was introduced into the antigen-free diet.

The findings of this study have clinical implications because the AFD components used in this study are similar to enteral nutritional components often used as adjunctive treatment for gastrointestinal cancers, especially in people with familial adenomatous polyposis and inflammatory bowel disease (IBD).