Paper Spotlight: Adaptor Protein Regulates Donor T Cell Migration



February 22, 2022

Oncotarget published this research paper in Volume 11, Issue 17, entitled, "CrkL is required for donor T cell migration to GvHD target organs" by researchers from the Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia Research Institute and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY. DOI - Correspondence to - Mobin Karimi - Abstract The success of cancer therapies based on allogeneic hematopoietic stem cell transplant relies on the ability to separate graft-versus-host disease (GvHD) from graft-versus-tumor (GVT) responses. Controlling donor T cell migration into peripheral tissues is a viable option to limit unwanted tissue damage, but a lack of specific targets limits progress on this front. Here, we show that the adaptor protein CrkL, but not the closely related family members CrkI or CrkII, is a crucial regulator of T cell migration. In vitro, CrkL-deficient T cells fail to polymerize actin in response to the integrin ligand ICAM-1, resulting in defective migration. Using a mouse model of GvHD/GVT, we found that while CrkL-deficient T cells can efficiently eliminate hematopoietic tumors they are unable to migrate into inflamed organs, such as the liver and small intestine, and thus do not cause GvHD. These results suggest a specific role for CrkL in trafficking to peripheral organs but not the lymphatic system. In line with this, we found that although CrkL-deficient T cells could clear hematopoietic tumors, they failed to clear the same tumor growing subcutaneously, highlighting the role of CrkL in controlling T cell migration into peripheral tissues. Our results define a unique role for CrkL in controlling T cell migration, and suggest that CrkL function could be therapeutically targeted to enhance the efficacy of immunotherapies involving allogeneic donor cells. Sign up for free Altmetric alerts about this article - Press release - Keywords - graft-versus-host disease, CrkL, T cell, migration, inflammation About Oncotarget Oncotarget is a peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit and connect with us: SoundCloud - Facebook - Twitter - Instagram - YouTube - LinkedIn - Pinterest - Reddit - Oncotarget is published by Impact Journals, LLC: Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

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