One of the frustrations of immunotherapy for cancer is that there is no one-size-fits-all drug. Most work well for some people but have little effect on other patients with the same type of cancer. This also applies to thenewer cancer treatmentsjust like for older types of chemotherapy. However, researchers at the Weizmann Institute of Science recently identified certain markers. These can be used to predict which patients have a better chance of a positive response to immunotherapy treatments.
Predicting the effect of immunotherapy in cancer
For Professor Yardena Samuels and her research group, this research is based on understanding which treatments are most likely to work. Accordingly, this could be the first step towards creating a personalized approach to healing orPrevention of cancerbe. The focus of her work is primarily on melanoma. This is a collection of skin cancers that are often difficult to treat and can consist of different tumor cells, as well as hundreds of different mutations.
In recent years, medicine has successfully treated a certain percentage of melanomas with cancer immunotherapy. These are known as immune checkpointsInhibitors known. They remove internal obstacles that trigger the body's immune system and prevent it from attacking the cancer. Unfortunately, these medications remain ineffective for others.
To understand the differences in response between different people, the research team first analyzed data from 470 patients. They were particularly interested in differences in survival rates.
Proteasomes are protein complexes that reduce long proteins into short pieces called peptides. The latter later appear on the cell surface through molecules that scientists call human leukocyte antigens (HLA). Such antigens are essentially small molecules that show up on the outside of cells and provide information about new threats that the immune system needs to assess and address.
Medical perspectives
The immunoprotein is assembled from modified subunits, creating a unique collection of HLA antigens. The team believed that a specific modification and overexpression of the peptides could lead to better recognition of tumor cells by the immune system and thus better elimination of cancer cells.
To test this idea, the researchers cultured lines of tumor cells from patients with melanoma cells. By testing the response of immune cells from the same patients, they showed that the newly formed peptides were actually more reactive than the HLA antigens. The experiments therefore showed that in tumor cells in which the subunits were overexpressed, the various components of the immune system that directly fight the cancer were more abundant and active than average.
Looking back at the details of the cancer patients in the database, the team reported that levels of the two subunits were excellent predictors of outcome. These biomarkers were better than the tumor mutation burden currently used in the clinic. The researchers in Samuels and Ruppin's lab beatin the studysuggested that immunoproteasome expression can be used as a biomarker for predicting better outcomes in melanoma.
