Arja Ray
725 N. Wolfe Street
Office - Physiology 107B
Lab - Physiology 104
Intricacies of Immune Cell Function in Tumors
Immunotherapy has revolutionized the treatment of cancer. Most modalities of cancer immunotherapy work by enabling cytotoxic CD8 T cells to recognize and kill cancer cells. These cells, however, do not work in isolation and are inextricably shaped by the aberrant tumor microenvironment (TME), which includes other immune cells such as macrophages and dendritic cells, as well as acellular components such as the extracellular matrix (ECM). We seek to understand the intrinsic and microenvironmental regulation of cytotoxic CD8 T cell function in the context of tumors. We take advantage of novel genetically engineered mouse models to mark specific states of T cells and macrophages, high dimensional immune profiling, live imaging, in vitro 3D ECM culture systems and a variety of other techniques.
Ray A., Bassette M., Hu, K.H., Samad B., Pass M., …, Krummel M.F.:
Multimodal delineation of a layer of effector function among exhausted CD8 T cells in tumors.
Science Immunology (Accepted provisionally; BioRxiv: 10.1101/2023.09.26.559470).
Ray A., Hu, K.H., Kersten K., Courau T., Kuhn N.F., Zaleta-Linares, I., Samad B., Combes A.J., Krummel M.F.: Targeting CD206+ macrophages disrupts the establishment of a key ant-tumor immune axis. J Exp Med (2025) 222 (1): e20240957 (On the Cover).
Combes A.J.*, Courau T.*, Kuhn N.F.*, Hu K.H.*, Ray A.*, Chen W.S., … , Krummel M. F.:
Global Absence and Targeting of Protective Immune States in Severe COVID-19.
Nature 591 (7848):124-130, 2021. (* co-first authors)
You R., Artichoker J., Ray A., Velozo H.G., Rock D.A., Conner K.P., Krummel M. F.:
Visualizing Spatial and Stoichiometric Barriers to Bispecific T cell Engager Efficacy.
Cancer Immunology Research, 10 (6): 698-712, 2022
Kersten K., Hu K.H., Combes A.J., Samad B., Harwin T., Ray A., … Krummel M.F.:
Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells in cancer.
Cancer Cell, 40 (6): 624-638.e9, 2022.
Ray A.*, Callaway M.K.*, Rodriguez-Merced N.J., Crampton A.L., Carlson M., Emme K.B., Ensminger E.A., Schrope, J.H., Rasmussen H.R., Jiang H., Denardo D.G., Wood D.K., Provenzano P.P.: Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma.
JCI Insight, 7(3): e150330, 2022 (* co-first authors)
Ray A., Lee O., Win Z., Edwards R.M., Alford P.W., Kim D.H., Provenzano P.P.:
Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration. Nature Communications 8:14923, 2017. Highlighted in F1000Prime: Reinhart-King C: F1000Prime Recommendation of [Ray A et al., Nat Commun 2017 8:14923]. In F1000Prime, 18 May 2017; 10.3410/f.727500138.793531872
Ray A., Slama Z.M., Morford R.K., Madden S.A., Provenzano P.P.: Enhanced directional migration of cancer stem cells in 3D aligned collagen matrices. Biophysical Journal, 112(5):1023-1036, 2017.
Ray A.*, Provenzano P.P.*: Aligned forces: Origins and mechanisms of cancer dissemination guided by ECM architecture. Current Opinion in Cell Biology 72 (63-71), 2021. (* co-corresponding authors)
Ray A., Morford R.K., Ghaderi N., Odde D.J., Provenzano P.P.: Dynamics of 3D carcinoma cell invasion into aligned collagen. Integrative Biology, 10(2): 100-112, 2018.
Ray A., Morford R.K., Provenzano P.P: Cancer stem cell migration in three-dimensional aligned collagen matrices. Current Protocols in Stem Cell Biology, e57, 2018.