Breakthrough for treating the deadliest skin cancer
An international study led by Prof. Carmit Levy has uncovered a previously unknown mechanism that helps melanoma evade the body's immune defenses. The findings, published in Cell, could open the door to new strategies for improving cancer immunotherapy.
Melanoma is one of the most aggressive forms of skin cancer. Although the immune system is often capable of recognizing melanoma cells, many patients fail to respond to immunotherapy. Until now, researchers did not fully understand how these tumors escape destruction by immune cells.
The researchers found that melanosomes are decorated by major histocompatibility complex (MHC) molecules that stimulate CD8+ T cells through their T cell receptor (TCR). These melanosomes attract cancer-fighting T cells, such that instead of attacking the tumor, the T cells bind to the melanosomes. As a result, the immune cells become less effective, lose energy, and may even die, allowing the cancer to grow unchecked. The study further showed that blocking melanosome release in mouse models increased the number of immune cells that infiltrated the tumor and significantly slowed tumor growth.
The findings reveal an entirely new way by which melanoma avoids immune attack and suggest that targeting melanosome production or release could enhance the effectiveness of existing immunotherapies. The research may ultimately help improve treatment outcomes for patients with melanoma and potentially other cancers that use similar immune-evasion strategies.
Read the full paper:
HLA export by melanoma cells decoys cytotoxic T cells to promote immune evasion
Published in: Cell
Authors: Yoav Chemla, Orit Itzhaki, Stav Melamed, Chen Weller, Yuval Sade, Paulee Manich, Keren Reshef, Nicolas Xenidis, Avishai Maliah, Gilad Levy, Roma Parikh, Osnat Bartok, Opal Levy, Itay Tal, Gal Aziel, Abraham Nissani, Sharon Yunger, Daniela Likonen, Vitaly Kliminsky, Tamar Golan, Coralie Capron, Valentina Ace, Ronen Levy, Diana Rasoulouniriana, Zohar Eyal, Yuval Barzilay, Roi Balaban, Aseel Khateeb, Rami Khosravi, Amir Grau, Tamar Ziv, Polina Greenberg, Dvir Netanely, Hananya Vaknin, Xunwei Wu, Yael Amitay, Ronen Brenner, Julia María Martínez Gómez, Dov Hershkovitz, Tal Yardeni, Valentina Zemser-Werner, Oren Kobiler, Yael Friedmann, David Bassan, Ron Shamir, Lea Eisenbach, Nadine Santana-Magal, Michael Milyavsky, Galit Eisenberg, Leeat Keren, Merav Cohen, Dvir Gur, Boaz Barak, Michal Lotem, David Sprinzak, Shoshana Greenberger, David Fisher, Michal J. Besser, Mehdi Khaled, Pierre Close, Ronnie Shapira, Sebastien Apcher, Asaf Madi, Mitchell P. Levesque, Francessca Rapino, Yaron Carmi, Shivang Parikh, Yardena Samuels, Carmit Levy
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