Research

Immunotherapy Response

LSP research aims to understand the tumor-immune microenvironment to inform strategies for wielding the immune system against cancer.

The immune system plays a critical role in recognizing and responding to tumors. Immunotherapy leverages this capacity, harnessing the immune system to kill tumor cells, and has led to transformative durable responses in some patients. Despite this promise, many tumors do not respond to immunotherapy for reasons that are not fully understood.

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. Our research aims to uncover how the tumor microenvironment contributes to immune modulation and evasion and use these insights to inform new clinical diagnostics and therapeutic strategies. So far, this work has revealed potential therapeutic targets and immune-based biomarkers that may predict response to treatment.

Sun, Y., Maggs, L., Panda, A., Wright, S. J., Cicerchia, A. M., Jenney, A., Perricone, M. D., Mills, C. E., Cattaneo, G., Ventin, M., Chen, F., Rasmussen, M. Q., Miranda, A., Revach, O.-Y., Fang, J., Fu, A., Bowling, P. J., Sharova, T., Lawless, A., … Jenkins, R. W. (2025). TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids. Cancer Immunology Research, 13(2), 210–228. https://doi.org/10.1158/2326-6066.CIR-23-1011

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

Wala, J., de Bruijn, I., Coy, S., Gagné, A., Chan, S., Chen, Y.-A., Hoffer, J., Muhlich, J., Schultz, N., Santagata, S., & Sorger, P. K. (2024). Integrating spatial profiles and cancer genomics to identify immune-infiltrated mismatch repair proficient colorectal cancers [Preprint]. bioRxiv. https://doi.org/10.1101/2024.09.24.614701

Maliga, Z., Kim, D. Y., Bui, A.-T. N., Lin, J.-R., Dewan, A. K., Jadeja, S., Murphy, G. F., Nirmal, A. J., Lian, C. G., Sorger, P. K., & LeBoeuf, N. R. (2024). Immune Profiling of Dermatologic Adverse Events from Checkpoint Blockade Using Tissue Cyclic Immunofluorescence: A Pilot Study. The Journal of Investigative Dermatology, 144(8), 1887-1890.e5. https://doi.org/10.1016/j.jid.2024.01.024

Ricciuti, B., Lamberti, G., Puchala, S. R., Mahadevan, N. R., Lin, J.-R., Alessi, J. V., Chowdhury, A., Li, Y. Y., Wang, X., Spurr, L., Pecci, F., Di Federico, A., Venkatraman, D., Barrichello, A. P., Gandhi, M., Vaz, V. R., Pangilinan, A. J., Haradon, D., Lee, E., … Awad, M. M. (2024). Genomic and Immunophenotypic Landscape of Acquired Resistance to PD-(L)1 Blockade in Non-Small-Cell Lung Cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 42(11), 1311–1321. https://doi.org/10.1200/JCO.23.00580

Coy, S., Lee, J. S., Chan, S. J., Woo, T., Jones, J., Alexandrescu, S., Wen, P. Y., Sorger, P. K., Ligon, K. L., & Santagata, S. (2024). Systematic characterization of antibody-drug conjugate targets in central nervous system tumors. Neuro-Oncology, 26(3), 458–472. https://doi.org/10.1093/neuonc/noad205

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

Sun, Y., Revach, O.-Y., Anderson, S., Kessler, E. A., Wolfe, C. H., Jenney, A., Mills, C. E., Robitschek, E. J., Davis, T. G. R., Kim, S., Fu, A., Ma, X., Gwee, J., Tiwari, P., Du, P. P., Sindurakar, P., Tian, J., Mehta, A., Schneider, A. M., … Jenkins, R. W. (2023). Targeting TBK1 to overcome resistance to cancer immunotherapy. Nature, 615(7950), 158–167. https://doi.org/10.1038/s41586-023-05704-6

Burger, M. L., Cruz, A. M., Crossland, G. E., Gaglia, G., Ritch, C. C., Blatt, S. E., Bhutkar, A., Canner, D., Kienka, T., Tavana, S. Z., Barandiaran, A. L., Garmilla, A., Schenkel, J. M., Hillman, M., de Los Rios Kobara, I., Li, A., Jaeger, A. M., Hwang, W. L., Westcott, P. M. K., … Jacks, T. (2021). Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors. Cell, 184(19), 4996-5014.e26. https://doi.org/10.1016/j.cell.2021.08.020

Liu, D., Lin, J.-R., Robitschek, E. J., Kasumova, G. G., Heyde, A., Shi, A., Kraya, A., Zhang, G., Moll, T., Frederick, D. T., Chen, Y.-A., Wang, S., Schapiro, D., Ho, L.-L., Bi, K., Sahu, A., Mei, S., Miao, B., Sharova, T., … Boland, G. M. (2021). Evolution of delayed resistance to immunotherapy in a melanoma responder. Nature Medicine, 27(6), 985–992. https://doi.org/10.1038/s41591-021-01331-8

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

Coy, S., Rashid, R., Lin, J.-R., Du, Z., Donson, A. M., Hankinson, T. C., Foreman, N. K., Manley, P. E., Kieran, M. W., Reardon, D. A., Sorger, P. K., & Santagata, S. (2018). Multiplexed immunofluorescence reveals potential PD-1/PD-L1 pathway vulnerabilities in craniopharyngioma. Neuro-Oncology, 20(8), 1101–1112. https://doi.org/10.1093/neuonc/noy035

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Research

Immunotherapy Response

LSP research aims to understand the tumor-immune microenvironment to inform strategies for wielding the immune system against cancer.

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