Research

Cancer Immunology

LSP researchers seek to understand how immune cells interact with tumors to identify new ways to prevent and treat cancer.

The immune system drives the body’s recognition of and response to tumors. In turn, tumors develop methods to evade the immune system, preventing immune cells from attacking the tumor. Tumors are highly heterogeneous, containing mixed and ever-evolving populations of cells, but it is not understood how these genetic or temporal variations impact interactions with the immune system.

LSP Investigators leverage spatial profiling methods like multiplexed imaging, spatial transcriptomics, and in vitro or in vivo models to understand the complex interactions between tumor and immune cells in cancer. We aim to uncover how the tumor microenvironment contributes to immune modulation and evasion and use these insights to inform new clinical diagnostics and therapeutics. This work has already revealed potential therapeutic targets and immune-based biomarkers that may predict response to treatment.

Oka, T., Hasegawa, T., Lee, T., Oliver-Garcia, V. S., Mortaja, M., Azin, M., Horiba, S., Smith, S. S., Khattab, S., Trerice, K. E., Chen, S. T., Semenov, Y. R., & Demehri, S. (2025). Langerhans Cells Directly Interact with Resident T Cells in the Human Epidermis. JID Innovations: Skin Science from Molecules to Population Health, 5(1), 100324. https://doi.org/10.1016/j.xjidi.2024.100324

Mollaoglu, G., Tepper, A., Falcomatà, C., Potak, H. T., Pia, L., Amabile, A., Mateus-Tique, J., Rabinovich, N., Park, M. D., LaMarche, N. M., Brody, R., Browning, L., Lin, J.-R., Zamarin, D., Sorger, P. K., Santagata, S., Merad, M., Baccarini, A., & Brown, B. D. (2024). Ovarian cancer-derived IL-4 promotes immunotherapy resistance. Cell, 187(26), 7492-7510.e22. https://doi.org/10.1016/j.cell.2024.10.006

Yapp, C., Nirmal, A. J., Zhou, F. Y., Wong, A. Y. H., Tefft, J., Lu, Y. D., Shang, Z., Maliga, Z., Montero Llopis, P., Murphy, G. F., Lian, C., Danuser, G., Santagata, S., & Sorger, P. K. (2023). Highly Multiplexed 3D Profiling of Cell States and Immune Niches in Human Tumours [Preprint]. bioRxiv. https://doi.org/10.1101/2023.11.10.566670

Smith, N. P., Yan, Y., Pan, Y., Williams, J. B., Manakongtreecheep, K., Pant, S., Zhao, J., Tian, T., Pan, T., Stingley, C., Wu, K., Zhang, J., Kley, A. L., Sorger, P. K., Villani, A.-C., & Kupper, T. S. (2023). Resident memory T cell development is associated with AP-1 transcription factor upregulation across anatomical niches [Preprint]. bioRxiv. https://doi.org/10.1101/2023.09.29.560006

Lin, J.-R., Chen, Y.-A., Campton, D., Cooper, J., Coy, S., Yapp, C., Tefft, J. B., McCarty, E., Ligon, K. L., Rodig, S. J., Reese, S., George, T., Santagata, S., & Sorger, P. K. (2023). High-plex immunofluorescence imaging and traditional histology of the same tissue section for discovering image-based biomarkers. Nature Cancer, 4(7), 1036–1052. https://doi.org/10.1038/s43018-023-00576-1

Gaglia, G., Burger, M. L., Ritch, C. C., Rammos, D., Dai, Y., Crossland, G. E., Tavana, S. Z., Warchol, S., Jaeger, A. M., Naranjo, S., Coy, S., Nirmal, A. J., Krueger, R., Lin, J.-R., Pfister, H., Sorger, P. K., Jacks, T., & Santagata, S. (2023). Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma. Cancer Cell, 41(5), 871-886.e10. https://doi.org/10.1016/j.ccell.2023.03.015

Lin, J.-R., Wang, S., Coy, S., Chen, Y.-A., Yapp, C., Tyler, M., Nariya, M. K., Heiser, C. N., Lau, K. S., Santagata, S., & Sorger, P. K. (2023). Multiplexed 3D atlas of state transitions and immune interaction in colorectal cancer. Cell, 186(2), 363-381.e19. https://doi.org/10.1016/j.cell.2022.12.028

Notarangelo, G., Spinelli, J. B., Perez, E. M., Baker, G. J., Kurmi, K., Elia, I., Stopka, S. A., Baquer, G., Lin, J.-R., Golby, A. J., Joshi, S., Baron, H. F., Drijvers, J. M., Georgiev, P., Ringel, A. E., Zaganjor, E., McBrayer, S. K., Sorger, P. K., Sharpe, A. H., … Haigis, M. C. (2022). Oncometabolite d-2HG alters T cell metabolism to impair CD8+ T cell function. Science (New York, N.Y.), 377(6614), 1519–1529. https://doi.org/10.1126/science.abj5104

Coy, S., Wang, S., Stopka, S. A., Lin, J.-R., Yapp, C., Ritch, C. C., Salhi, L., Baker, G. J., Rashid, R., Baquer, G., Regan, M., Khadka, P., Cole, K. A., Hwang, J., Wen, P. Y., Bandopadhayay, P., Santi, M., De Raedt, T., Ligon, K. L., … Santagata, S. (2022). Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma. Nature Communications, 13(1), 4814. https://doi.org/10.1038/s41467-022-32430-w

Nirmal, A. J., Maliga, Z., Vallius, T., Quattrochi, B., Chen, A. A., Jacobson, C. A., Pelletier, R. J., Yapp, C., Arias-Camison, R., Chen, Y.-A., Lian, C. G., Murphy, G. F., Santagata, S., & Sorger, P. K. (2022). The spatial landscape of progression and immunoediting in primary melanoma at single-cell resolution. Cancer Discovery, 12(6), 1518–1541. https://doi.org/10.1158/2159-8290.CD-21-1357

Wang, Q., Bergholz, J. S., Ding, L., Lin, Z., Kabraji, S. K., Hughes, M. E., He, X., Xie, S., Jiang, T., Wang, W., Zoeller, J. J., Kim, H.-J., Roberts, T. M., Konstantinopoulos, P. A., Matulonis, U. A., Dillon, D. A., Winer, E. P., Lin, N. U., & Zhao, J. J. (2022). STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer. Nature Communications, 13(1), 3022. https://doi.org/10.1038/s41467-022-30568-1

Launonen, I.-M., Lyytikäinen, N., Casado, J., Anttila, E. A., Szabó, A., Haltia, U.-M., Jacobson, C. A., Lin, J. R., Maliga, Z., Howitt, B. E., Strickland, K. C., Santagata, S., Elias, K., D’Andrea, A. D., Konstantinopoulos, P. A., Sorger, P. K., & Färkkilä, A. (2022). Single-cell tumor-immune microenvironment of BRCA1/2 mutated high-grade serous ovarian cancer. Nature Communications, 13(1), 835. https://doi.org/10.1038/s41467-022-28389-3

Mehta, A. K., Cheney, E. M., Hartl, C. A., Pantelidou, C., Oliwa, M., Castrillon, J. A., Lin, J.-R., Hurst, K. E., de Oliveira Taveira, M., Johnson, N. T., Oldham, W. M., Kalocsay, M., Berberich, M. J., Boswell, S. A., Kothari, A., Johnson, S., Dillon, D. A., Lipschitz, M., Rodig, S., … Guerriero, J. L. (2021). Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer. Nature Cancer, 2(1), 66–82. https://doi.org/10.1038/s43018-020-00148-7

Goldberg, J., Pastorello, R. G., Vallius, T., Davis, J., Cui, Y. X., Agudo, J., Waks, A. G., Keenan, T., McAllister, S. S., Tolaney, S. M., Mittendorf, E. A., & Guerriero, J. L. (2021). The immunology of hormone receptor positive breast cancer. Frontiers in Immunology, 12, 674192. https://doi.org/10.3389/fimmu.2021.674192

Ringel, A. E., Drijvers, J. M., Baker, G. J., Catozzi, A., García-Cañaveras, J. C., Gassaway, B. M., Miller, B. C., Juneja, V. R., Nguyen, T. H., Joshi, S., Yao, C.-H., Yoon, H., Sage, P. T., LaFleur, M. W., Trombley, J. D., Jacobson, C. A., Maliga, Z., Gygi, S. P., Sorger, P. K., … Haigis, M. C. (2020). Obesity shapes metabolism in the tumor microenvironment to suppress anti-tumor immunity. Cell, 183(7), 1848-1866.e26. https://doi.org/10.1016/j.cell.2020.11.009

Izar, B., Tirosh, I., Stover, E. H., Wakiro, I., Cuoco, M. S., Alter, I., Rodman, C., Leeson, R., Su, M.-J., Shah, P., Iwanicki, M., Walker, S. R., Kanodia, A., Melms, J. C., Mei, S., Lin, J.-R., Porter, C. B. M., Slyper, M., Waldman, J., … Regev, A. (2020). A single-cell landscape of high-grade serous ovarian cancer. Nature Medicine, 26(8), 1271–1279. https://doi.org/10.1038/s41591-020-0926-0

Färkkilä, A., Gulhan, D. C., Casado, J., Jacobson, C. A., Nguyen, H., Kochupurakkal, B., Maliga, Z., Yapp, C., Chen, Y.-A., Schapiro, D., Zhou, Y., Graham, J. R., Dezube, B. J., Munster, P., Santagata, S., Garcia, E., Rodig, S., Lako, A., Chowdhury, D., … Konstantinopoulos, P. A. (2020). Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer. Nature Communications, 11(1), 1459. https://doi.org/10.1038/s41467-020-15315-8

Jerby-Arnon, L., Shah, P., Cuoco, M. S., Rodman, C., Su, M.-J., Melms, J. C., Leeson, R., Kanodia, A., Mei, S., Lin, J.-R., Wang, S., Rabasha, B., Liu, D., Zhang, G., Margolais, C., Ashenberg, O., Ott, P. A., Buchbinder, E. I., Haq, R., … Regev, A. (2018). A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell, 175(4), 984-997.e24. https://doi.org/10.1016/j.cell.2018.09.006

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Research

Cancer Immunology

LSP researchers seek to understand how immune cells interact with tumors to identify new ways to prevent and treat cancer.

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