New method allows characterizing immune cells into tumor tissue -
Despite recent achievements in the development of cancer immunotherapies, only a small group of patients usually meet them. The predictors of course and response to immunotherapy of diseases are urgently needed. To meet this need, researchers at the Tisch Cancer Institute (TCI) at Mount Sinai Icahn School of Medicine have developed a new marker analysis method of multiple tissues using a single blade of a section tumor to better understand the immune response occurring locally. MICSSS appointed for consecutive multiplexed immunohistochemistry staining on a single slide, the new technique allows characterizing human cells involved in immune responses at the site of tissue before and after treatment with immunotherapy. The research, published today in the journal Science Immunology , can help to identify new biomarkers to predict patient outcomes.
In cancer, having a measurable immune response at the tumor site has been associated with improved outcomes for patients with various cancers. Recent studies have shown that immune cells infiltrating the tumor consist of different subtypes with distinct functions, and their frequency, location and organization in cancerous tissues end up either promote anti-tumor immunity or, in some cases, preventing; both possibly affect patient outcomes. However, a lack of methods to characterize the complex relationships between immune cells and cancer and the difficulty of obtaining enough tissue to do with standard methods hinders the ability to investigate the mechanisms involved.
"Our goal was to get a better understanding of the immune responses to the tumor site while meeting the need for large analysis using the least amount of tissue," said Sacha Gnjatic, PhD, Associate Professor immunology, hematology and medical oncology at TCI, who was the co-lead author of the study with Miriam Merad, MD, PhD, professor of oncological sciences, hematology and medical oncology at TCI. "We need more comprehensive analyzes of immune tumor microenvironment, as part of our immune surveillance to inform treatment and predict outcomes for cancer patients."
The lead author Romain Note, PhD, a postdoctoral fellow working in the laboratory of Dr. Gnjatic and Dr. Merad, helped develop a new method to look at markers of multiple tissues and detect the expression of markers with a single biological tissue cutting blade. Researchers have applied the technique of MICSSS to tumor tissue sections melanoma cancer and lung cancer. This allowed the views of co-expression of markers on the same cells as the material from tissue sparing.
"MICSSS technique helps us to characterize the distribution of subsets of complex cells in tumor tissues without cross reactivity between the color cycles," Dr. Note said. "Unlike other available methods, our approach is not as dependent reagents or property instruments and should be easier to adapt because it follows the same staining steps being implemented in all pathology laboratories."
If the method of MICSSS has proven successful in other types of mapping tumors (hepatocellular carcinoma, colorectal, breast, head and neck, or pancreas), the researchers believe that it could be useful beyond just cancer. It provides the ability to reuse a slide from a tissue sample, up to 10 times, and characterize many parameters with standard chromogenic color. Researchers have begun to apply MICSSS to characterize the immune markers and tissues of diabetes, HIV-related renal disease, inflammatory bowel disease, and atherosclerosis.
"We hope to implement MICSSS in the human immune monitoring center TCI to characterize the types of immune cells infiltrating various cancers and other diseases to their density, location in the fabric, and diversity, "said Dr. Merad.
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