Mount Sinai Researchers Develop Simple Method to Characterize Immune Cells in Tumors
Despite recent achievements in the development of cancer immunotherapies, only a small group of patients typically respond to them. Predictive markers of disease course and response to immunotherapy are urgently needed. To address this need, researchers at The Tisch Cancer Institute (TCI) at the Icahn School of Medicine at Mount Sinai have developed a new method of analyzing multiple tissue markers using only one slide of a tumor section to better understand immune response occurring locally. Named MICSSS, for multiplexed immunohistochemical consecutive staining on a single slide, the new technique helps characterize human cells involved in immune responses at the tissue site, before and after treatment with immunotherapy. The research, published today in the journal Science Immunology, may help define new biomarkers to predict patient outcome.
In cancer, having a measurable immune response at the tumor site has been associated with improved outcome of patients with various types of cancers. Recent studies have shown that tumor-infiltrating immune cells consist of different subtypes with distinct functions, and that their frequency, localization, and organization in cancer tissues end up either promoting antitumor immunity or, in some cases, preventing it; both of these eventually affect the patient’s outcome. However, a lack of methods to characterize the complex relationships between immune and cancer cells and the difficulty of obtaining enough tissue to do so with standard methods hampers the ability to study the mechanisms at play.
“Our goal was to get a better understanding of immunologic responses at the tumor site while addressing the need for high-dimensional analysis using as little tissue as possible,” said Sacha Gnjatic, PhD, Associate Professor of Immunology, Hematology, and Medical Oncology at TCI, who was the senior co-author of this study with Miriam Merad, MD, PhD, Professor of Oncological Sciences, Hematology, and Medical Oncology at TCI. “We need more comprehensive analyses of the immune microenvironment of tumors, as part of our immune monitoring to inform treatment and predict outcomes for cancer patients.”
Lead author Romain Remark, PhD, a postdoctoral fellow working in the laboratories of Dr. Gnjatic and Dr. Merad, helped develop a new method to look at multiple tissue markers and detect expression of biological markers with just one tissue section slide. Researchers applied the MICSSS technique to tumor tissue sections of melanoma and lung cancers. This enabled views of co-expression of markers on the same cells while sparing material from tissues.
“The MICSSS technique helps us characterize the distribution of complex cell subsets in tumor tissues without cross-reactivity between staining cycles,” said Dr. Remark. “In contrast to other available methods, our approach is not as reliant on proprietary reagents or instruments and should be easier to adapt because it follows the same staining steps currently implemented throughout all pathology labs.”
If the MICSSS method is proven successful in mapping other tumor types (hepatocellular carcinoma, colorectal, breast, head and neck, or pancreatic cancers), the investigators believe it may be useful beyond just cancer. It offers the ability to reuse any slide from a tissue sample, up to 10 times, and to characterize multiple parameters with standard chromogen staining. Researchers have begun to apply MICSSS to characterize immune and tissue markers of diabetes, HIV-related kidney pathology, inflammatory bowel disease, and atherosclerosis.
“We hope to implement MICSSS as part of the Human Immune Monitoring Center at TCI to characterize the types of immune cells infiltrating various cancers and other disease for their density, localization in the tissue, and diversity,” said Dr. Merad.
Collaborators included researchers from Memorial Sloan Kettering Cancer Center in New York, the University of Heidelberg in Germany, and the Paris Descartes University in France.
The researchers declare no conflicts of interest.
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services—from community-based facilities to tertiary and quaternary care.
The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is in the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals."