Longitudinal Intravascular Antibody Labeling Identified Regulatory T Cell Recruitment as a Therapeutic Target in a Mouse Model of Lung Cancer.

Autor:	Shanahan SL; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA., Kunder N; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX., Inaku C; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX., Hagan NB; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX., Gibbons G; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA., Mathey-Andrews N; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.; Harvard Medical School, Boston, MA., Anandappa G; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX., Soares S; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA., Pauken KE; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX., Jacks T; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA., Schenkel JM; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA.; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.; Harvard Medical School, Boston, MA.; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX.; Department of Pathology, Brigham and Women's Hospital, Boston, MA.; Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Sep 15; Vol. 213 (6), pp. 906-918.
DOI:	10.4049/jimmunol.2400268
Abstrakt:	Anticancer immunity is predicated on leukocyte migration into tumors. Once recruited, leukocytes undergo substantial reprogramming to adapt to the tumor microenvironment. A major challenge in the field is distinguishing recently recruited from resident leukocytes in tumors. In this study, we developed an intravascular Ab technique to label circulating mouse leukocytes before they migrate to tissues, providing unprecedented insight into the kinetics of recruitment. This approach unveiled the substantial role of leukocyte migration in tumor progression using a preclinical mouse model of lung adenocarcinoma. Regulatory T cells (Tregs), critical mediators of immunosuppression, were continuously and rapidly recruited into tumors throughout cancer progression. Moreover, leukocyte trafficking depended on the integrins CD11a/CD49d, and CD11a/CD49d blockade led to significant tumor burden reduction in mice. Importantly, preventing circulating Treg recruitment through depletion or sequestration in lymph nodes was sufficient to decrease tumor burden, indicating that Treg migration was crucial for suppressing antitumor immunity. These findings underscore the dynamic nature of the immune compartment within mouse lung tumors and demonstrate the relevance of a temporal map of leukocyte recruitment into tumors, thereby advancing our understanding of leukocyte migration in the context of tumor development. (Copyright © 2024 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu