New study finds that location of immune cells is critical for immunotherapy response

New imaging technology has helped researchers from the Marathon of Hope Cancer Centres Network’s Quebec consortium (MOH-Q) determine that the spatial distribution of immune cells within melanoma can predict how well a patient will respond to immunotherapy. The findings, published in the cover of Science Immunology and led by a team at McGill University’s Rosalind and Morris Goodman Cancer Institute (GCI), could help personalize treatments for patients diagnosed with this form of skin cancer.

Led by Dr. Ian Watson, the research team used Imaging Mass Cytometry (IMC), a new technique that retains spatial information about cell distribution in cancerous tumours, to analyze 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.

“This 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,” says Dr. Watson, an investigator in the Cancer Research Program of the Research Institute of the McGill University Health Centre (RI-MUHC), and associate professor in the Department of Biochemistry at McGill University. “This 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.”

“Critically, we identified a subtype of T-cells whose abundance informed on a patient’s response to immune therapy,” says LeeAnn Ramsay, M.Sc., one of three co-first authors who equally contributed to this work and a research assistant with Dr. Watson.

“We 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,” explains co-first author Dr. Dan Moldoveanu, MD, and a PhD candidate supervised by Dr Watson and Dr. Sarkis Meteressian, MD, in the Department of Surgery at McGill University.

The researchers found that not only was the abundance of these T-cells important, but also their spatial organization within the tumour. “Furthermore, tumours in which antigen-experienced cytotoxic T-cells were situated in close proximity to tumour cells had higher rates of response to these agents,” says co-first author Mathieu Lajoie, PhD, a research associate with Dr. Watson.

More than 50 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'Université de Montréal, Hôpital Maisonneuve-Rosemont, the Lady Davis Institute at the Jewish General Hospital, McGill Genome Centre, McGill University Health Centre, Montreal Neurological Institute and Hospital, and numerous sites in the United States.

“Pre-treatment stratification of advanced melanoma patients according to their likelihood of response to immune checkpoint inhibitors remains an elusive goal in precision medicine,” says Dr. Catalin Mihalcioiu, MD, a medical oncologist at the McGill University Health Centre and a co-author of the study.

“Further 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,” concludes Dr. Watson.

This story has been written based on a press release provided by the Rosalind and Morris Goodman Cancer Institute and RI-MUHC.

Study

Spatially mapping the immune landscape of melanoma using imaging mass cytometry

Authors

Dan Moldoveanu, LeeAnn Ramsay,  Mathieu Lajoie, Luke Anderson-Trocme, Marine Lingrand, Diana Berry, Lucas J.M. Perus, Yuhong Wei, Cleber Moraes, Rached Alkallas, Shivshankari Rajkumar, Dongmei Zuo, Matthew Dankner, Eric Hongbo Xu, Nicholas R. Bertos, Hamed S. Najafabadi, Simon Gravel, Santiago Costantino, Martin J. Richer, Amanda W. Lund, Sonia V. Del Rincon, Alan Spatz, Wilson H. Miller Jr., Rahima Jamal, Réjean Lapointe, Anne-Marie Mes-Masson, Simon Turcotte, Kevin Petrecca, Sinziana Dumitra, Ari-Nareg Meguerditchian, Keith Richardson, Francine Tremblay, Beatrice Wang, May Chergui, Marie-Christine Guiot, Kevin Watters, John Stagg, Daniela F. Quail, Catalin Mihalcioiu, Sarkis Meterissian, Ian R. Watson

Funding

This study was partially funded by the Montreal Cancer Consortium Pilot for the Marathon of Hope Cancer Centres Network