Comparing the immune landscapes of HPV-induced tumors arising in the cervix (CxCa) or oropharynx (OPSCC), Saskia et al. found that despite similarities in PBMCs, immune infiltrates differed between anatomical locations, with immune profiles closely resembling that of the tissue of origin. CxCa tumors were more infiltrated by CD8+CD103+ and activated CD8+CD103+CD161+ effector T cells, while OPSCC tumors were more infiltrated by B cells, naive CD4+, and CD4+CD161+ effector memory T cells, and had a higher CD4:CD8 ratio. In OPSCC, but not CxCa, infiltration by CD4+ T cells or HPV-specific T cells correlated with survival.
PURPOSE: The tumor immune microenvironment determines clinical outcome. Whether the original tissue in which a primary tumor develops influences this microenvironment is not well understood. EXPERIMENTAL DESIGN: We applied high-dimensional single-cell mass cytometry (CyTOF) analysis and functional studies to analyze immune cell populations in human papillomavirus (HPV)-induced primary tumors of the cervix (CxCa) and oropharynx (OPSCC). RESULTS: Despite the same etiology of these tumors, the composition and functionality of their lymphocytic infiltrate substantially differed. CxCa displayed a 3-fold lower CD4:CD8 ratio, contained more activated CD8+CD103+CD161+ effector T-cells and less CD4+CD161+ effector memory T-cells than OPSCC. CD161+ effector cells produced the highest cytokine levels among tumor-specific T-cells. Differences in CD4+ T-cell infiltration between CxCa and OPSCC were reflected in the detection rate of intratumoral HPV-specific CD4+ T-cells and in their impact on OPSCC and CxCa survival. The PBMC composition of these patients, however, was similar. CONCLUSIONS: The tissue of origin significantly impacts the overall shape of the immune infiltrate in primary tumors.
Author Info: (1) Medical Oncology, Leiden University Medical Center s.j.a.m.santegoets@lumc.nl. (2) Clinical Oncology, Leiden University Medical Center. (3) Medical Oncology, Leiden University
Author Info: (1) Medical Oncology, Leiden University Medical Center s.j.a.m.santegoets@lumc.nl. (2) Clinical Oncology, Leiden University Medical Center. (3) Medical Oncology, Leiden University Medical Center. (4) Department of Medical Oncology, National Center for Tumor Diseases, University Medical Center Heidelberg. (5) Medical Oncology, Leiden University Medical Center. (6) Immunohematology and Blood Bank, Leiden University Medical Center. (7) Computational Biology Center, Leiden University Medical Center. (8) Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center. (9) Otorhinolaryngology and Head and Neck Surgery, Leiden University Medical Center. (10) Gynecology, Leiden University Medical Center. (11) Gynecology, Leids University medical Center. (12) Gynecology, Leiden University Medical Center. (13) Medical Oncology, Leiden University Medical Center. (14) Medical Oncology, Leiden University Medical Center.
