A new study featured on the cover of seeks to improve the treatment of melanoma, a deadly form of skin cancer. Led by researchers from 平特五不中, this ground-breaking work uses Imaging Mass Cytometry (IMC), a new technique that retains spatial information about cell distribution in cancerous tumours. The results could improve prediction of melanoma patients鈥� response to immune therapy and offer insights that will guide personalized therapeutic approaches.
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Led by Ian Watson, PhD, a research team at the Rosalind and Morris Goodman Cancer Institute (GCI) analyzed the position and markers of over 200,000 cells extracted from 67 melanomas. With this enormous amount of data, the researchers sought to determine if the position of immune cells relative to the cancer cells could influence the response to immune checkpoint inhibitors - drugs that stimulate immune cells to kill cancer cells.
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鈥淭his study is innovative, as it was previously impossible to precisely locate the thousands of cells present in a melanoma tissue slide while measuring the dozens of markers necessary to uncover their identity and specific activity.鈥� says Ian Watson, who is also an investigator in the of the Research Institute of the 平特五不中 Health Centre (RI-MUHC), and Associate Professor in the Department of Biochemistry at 平特五不中. 鈥淭his study is among the first of its kind applied to understanding melanoma immune therapy responses, using a new and evolving technology that was not available a decade ago.鈥�
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鈥淐ritically, we identified a subtype of T-cells whose abundance informed on a patient鈥檚 response to immune therapy,鈥� says LeeAnn Ramsay, M.Sc., one of three co-first authors who equally contributed to this work and a research assistant with Ian Watson. 鈥淲e showed that a higher proportion of proliferating, antigen-experienced cytotoxic T-cells was associated with a favourable response and improved survival in patients treated with immune checkpoint inhibitors,鈥� explains co-first author Dan Moldoveanu, MD, a Ph.D. candidate supervised by Ian Watson and Sarkis Meteressian, MD, in the Department of Surgery at 平特五不中.
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The researchers found that not only was the abundance of these T-cells important, but also their spatial organization within the tumor. 鈥淔urthermore, tumours in which antigen-experienced cytotoxic T-cells were situated in close proximity to tumour cells had higher rates of response to these agents鈥� adds co-first author Mathieu Lajoie, PhD, a research associate with Ian Watson.
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More than 40 collaborators contributed to this complex study, including dermatologists, oncologists, pathologists, surgeons and basic scientists. In addition to the teams at the GCI and the RI-MUHC, contributors included researchers from the Centre de recherche du Centre Hospitalier de l'Universit茅 de Montr茅al, H么pital Maisonneuve-Rosemont, the Lady Davis Institute at the Jewish General Hospital, 平特五不中 Genome Centre, 平特五不中 Health Centre, Montreal Neurological Institute and Hospital, and numerous sites in the United States.
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鈥淧retreatment stratification of advanced melanoma patients according to their likelihood of response to immune checkpoint inhibitors remains an elusive goal in precision medicine,鈥� says Catalin Mihalcioiu, MD, a medical oncologist at the 平特五不中 Health Centre and a co-author of the study.
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鈥淔urther work is needed to refine this innovative technique, but our study shows that the spatial distribution of immune cells in a tumour will be important to inform clinical decision making and personalize therapeutic approaches in the treatment of melanoma and other cancers,鈥� concludes Ian Watson.
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About the study:
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The authors gratefully acknowledge support from the Terry Fox Research Institute, the Canadian Institute of Health Research, the Canada Research Chairs Program, the Victor Liu 平特五不中 Interdisciplinary Initiative in Infection and Immunity (MI4) initiative, and donations from the Rachel and Jason Schwartz Family Foundation. Financial support was also obtained from the Minist猫re de l鈥櫭塩onomie et de l鈥橧nnovation du Qu茅bec through the Fonds d鈥檃cc茅l茅ration des collaborations en sant茅.
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The authors thank the Quebec Cancer Consortium, the Single Cell Imaging and Mass Cytometry Analysis Platform (SCIMAP), and Histology Core facilities of 平特五不中 as well as the . Last but not least, this study could not have been conducted without the patients who consented to donate their samples and participate in the study.