The ratio of cytotoxic lymphocytes to M2-like macrophages is prognostic in immunogenic tumors

Mezheyeuski, A.; Backman, M.; Mattsson, J.; Martin-Bernabe, A.; Larsson, C.; Hrynchyk, I.; Hammarström, K.; Ström, S.; Ekström, J.; Mauchanski, S.; Khelashvili, S.; Agnarsdottir, M.; Edqvist, P.-H.; Huvila, J.; Segersten, U.; Malmström, P.-U.; Botling, J.; Nodin, B.; Hedner, C.; Borg, D.; Bärndstedt, J.; Sartor, H.; Leandersson, K.; Glimelius, B.; Portyanko, A.; Ponten, F.; Jirström, K.; Micke, P.; Sjöblom, T.

doi:10.1101/2021.03.24.436814

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bioRxiv · 10.1101/2021.03.24.436814

The ratio of cytotoxic lymphocytes to M2-like macrophages is prognostic in immunogenic tumors

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Abstract

Immune cells in the microenvironment shape tumor development and progression. The prognostic value of T-cell-based immune scores exceeds those of clinical parameters in colon cancer, but reflects only a part of the anti-tumor immune response. Here, we assessed 15 distinct immune cell classes and identified a simple prognostic signature based on pro- and anti-tumoral immune cells in the tumor microenvironment. The ratio of cytotoxic lymphocytes to tumor supportive macrophages predicted survival better than the state-of-art immune score in colon cancer and had the highest relative contribution to survival prediction when compared to established clinical parameters. This signature was prognostic also in other cancers with high mutation burden, such as those of the lung, bladder, esophagus, and melanomas, supporting broad clinical applicability. One Sentence SummaryThe CD8/M2 ratio in tumor tissue defines prognosis in immunogenic cancers

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Mezheyeuski, A., Backman, M., Mattsson, J., Martin-Bernabe, A., Larsson, C., Hrynchyk, I., Hammarström, K., Ström, S., Ekström, J., Mauchanski, S., Khelashvili, S., Agnarsdottir, M., Edqvist, P.-H., Huvila, J., Segersten, U., Malmström, P.-U., Botling, J., Nodin, B., Hedner, C., Borg, D., Bärndstedt, J., Sartor, H., Leandersson, K., Glimelius, B., Portyanko, A., Ponten, F., Jirström, K., Micke, P., Sjöblom, T.. 2021-03-24. The ratio of cytotoxic lymphocytes to M2-like macrophages is prognostic in immunogenic tumors. https://doi.org/10.1101/2021.03.24.436814

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