Bacterial peptides that exist on tumor cells may be immunotherapy targets. Research has shown that protein fragments from bacteria that invade tumor cells may be on the surface of the tumor cell, and the immune system may recognize those protein fragments. This discovery may advance certain cancer immunotherapies.
Microorganisms colonize on human tumors. These colonies are called the tumor microbiota, which impacts the microenvironment of the tumor like causing local immunosuppression or inflammation. This may alter how the body’s immune system responds to the tumor, which in turn may change responses to treatment. But, are the bacteria within a tumor recognized by the immune system? New research suggests that bacterial protein fragments known as peptides may exist on the surface of tumor cells. Immune cells called T cells recognize these peptides. This discovery may lead to advancements in cancer immunotherapeutics.
Identification of Bacteria-Derived HLA-Bound Peptides
Molecules known as tumor antigens enable the immune system to differentiate healthy cells from tumor cells. Each cell has antigen-producing mechanisms, which present antigen-derived peptides to be presented to the immune system via molecules called human leukocyte antigens (HLAs). These specialized molecules are called epitopes.
Tumor antigens fall into two primary categories: tumor-associated and tumor-specific. Tumor-associated antigens are found in normal tissue in addition to tumors. Hence, they do not trigger an immune response. But if an immune response does initiate, there is a risk of harmful autoimmune reactions against the normal tissues that have the tumor-associated antigen.
Because these tumor-associated antigens are found in many types of cancer tumors, they may be effective targets for immunotherapies. In contrast, tumor-specific antigens are found only in tumor cells, which makes them targets for specific immune attacks against the tumor.
A subtype, neoantigens, results from tumor-specific gene mutations. Thus, neoantigens are specific to both the tumor and patient. Targeting neoantigen-derived peptides (neopeptides) may enable scientists to develop personalized immunotherapies.
Melanoma has three types of tumor-associated antigens, and this skin cancer typically has many genetic mutations. This increases the likelihood of neoantigens. Therefore, melanoma has been the subject of tumor-antigen discovery and cancer-immunotherapy development.
Fighting Cancer and Infection
The researchers of this study investigated the bacterial composition of 17 melanoma metastases from 9 patients. They found that the composition of the bacteria was closely similar in different metastases from the same individual, and sometimes in samples from different people.
This suggests that a specific bacterial species may be common to melanoma, which supports a previous study that found tumor microbiota specific to different types of cancer. The scientists also found that the bacteria existed in melanoma cells as opposed to in the surrounding extracellular microenvironment.
They investigated whether peptides from the intracellular bacteria are presented to the immune system in the same way as are other intracellular antigens. They utilized mass spectrometry to find direct detection of HLA-presented peptides. They discovered nearly 300 peptides from 33 bacterial species. In addition, they found several peptides on multiple tumors from the same patient and in tumors from different patients.
Next the researchers looked into whether melanoma cells present the peptides to the immune system instead of immune cells. They used an immune-cell marker protein to separate cells into antigen-presenting cells (APCs) and tumor cells. They found both groups of cells presented bacterial peptides. And they showed that T cells separated from the melanomas reacted to the bacterial peptides, including some that were shared between the tumors and individual patients.
Final Thoughts
The bacterial peptides discovered by this new study could be effective targets for immunotherapy. It may prove to be relatively easy to induce a strong immune response against bacterial peptides, and there would be little concerns regarding autoimmunity if the bacterial peptides are not presented on normal tissues.
In essence, tumor-associated bacterial peptides could be used as tumor-specific antigens shared between individuals. This would be an advancement for therapeutics, which currently is seen only in viral-induced tumors that have epitopes derived from viral cancer-causing proteins. The recent work may be a foundation for pinpointing shared tumor-specific antigens across a wide array of tumor types.