Haist and Baertsch et al. studied the impact of tumor cell colonization of lymph nodes (LN) in patients with HNSCC and in a LN metastasis melanoma model. Primary tumors and paired LNs of node-positive patients showed an enrichment of spatially organized niches of immunosuppressive myeloid cells and CAFs that extended to adjacent tumor-free LNs, were absent in non-cancer patients, and were associated with T cell dysfunction. In the mouse model, LN colonization led to myeloid–CAF niches linked to T cell dysfunction (PD-L1hi CD86low) and Treg activation, suggesting LN colonization was an active driver of systemic immunosuppression.
Contributed by Katherine Turner
ABSTRACT: Lymph node (LN) colonization in cancer is linked to poor prognosis. Evidence suggests that LN colonization induces systemic immunosuppression, facilitating distant metastasis. We investigated LN-mediated immunosuppression in patients with head-and-neck cancer using spatial proteomics, spatial transcriptomics, and an in vivo model of melanoma LN metastasis. Both primary tumors and paired LNs of nodal-positive patients exhibit enhanced interferon-γ signaling and an enrichment of immunosuppressive myeloid cells and cancer-associated fibroblasts (CAFs). The spatial intersection of these myeloid-CAF-enriched niches with perifollicular T cell zones and LN follicles is linked to enhanced T cell dysfunction and Treg activation therein, thereby driving architectural LN remodeling. These immune suppressive changes extend to adjacent non-tumor-involved LN regions and nearby tumor-free LNs, but were not detected in LNs of non-cancer patients, reflecting a systemic effect that compromises anti-tumor immunity beyond the tumor-involved LN. Hence, our findings establish LN colonization as an active driver of systemic immunosuppression, facilitating metastatic progression.
Author Info: 1- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA 2- Department of Pathology, Stanford University School of Medicine, Stanford
Author Info: 1- Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA 2- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA 3- Department of Dermatology, University Medical Center Mainz, Mainz, Germany 4- Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany 5- Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany 6- Department of Otolaryngology, Stanford University, Stanford, CA, USA 7- Molecular Biosciences/Cancer Biology Program, Heidelberg University, Heidelberg, Germany 8- German Cancer Research Center, DKFZ, Heidelberg, Germany 9- Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany 10- Stanford Cancer Institute, Stanford University, Stanford, CA, USA 11- Department of Biomedical Data Science, Stanford University, Stanford, CA, USA 12- Departments of Biological Sciences and Computer Science, Purdue University, West Lafayette, IN, USA 13- Department of Radiation Oncology, Stanford University, Stanford, CA, USA 14- Department of Pathology, University Medical Center Mainz, Mainz, Germany 15- Department of Radiation Oncology and Radiotherapy, University Medical Center Mainz, Mainz, Germany 16- Department of Medicine, Stanford University, Stanford, CA, USA 17- Department of Radiology, Stanford University, Stanford, CA, USA 18- Department of Biomedical Engineering, Duke University, Durham, NC, USA 19- These authors contributed equally 20- Lead contact
