TY - JOUR
T1 - The anatomical location shapes the immune infiltrate in tumors of same etiology and affects survival
AU - Santegoets, Saskia J.
AU - van Ham, Vanessa J.
AU - Ehsan, Ilina
AU - Charoentong, Pornpimol
AU - Duurland, Chantal L.
AU - van Unen, Vincent
AU - Hollt, Thomas
AU - van der Velden, Lilly Ann
AU - van der Burg, Sjoerd H.
AU - More Authors, null
PY - 2019
Y1 - 2019
N2 - 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 [Cytometry by Time-Of-Flight (CyTOF)] analysis and functional studies to analyze immune cell populations in human papillomavirus (HPV)–induced primary tumors of the cervix (cervical carcinoma) and oropharynx (oropharyngeal squamous cell carcinoma, OPSCC). Results: Despite the same etiology of these tumors, the composition and functionality of their lymphocytic infiltrate substantially differed. Cervical carcinoma displayed a 3-fold lower CD4:CD8 ratio and contained more activated CD8þCD103þCD161þ effector T cells and less CD4þCD161þ effector memory T cells than OPSCC. CD161þ effector cells produced the highest cytokine levels among tumor-specific T cells. Differences in CD4þ T-cell infiltration between cervical carcinoma and OPSCC were reflected in the detection rate of intratumoral HPV-specific CD4þ T cells and in their impact on OPSCC and cervical carcinoma survival. The peripheral blood mononuclear cell composition of these patients, however, was similar. Conclusions: The tissue of origin significantly affects the overall shape of the immune infiltrate in primary tumors.
AB - 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 [Cytometry by Time-Of-Flight (CyTOF)] analysis and functional studies to analyze immune cell populations in human papillomavirus (HPV)–induced primary tumors of the cervix (cervical carcinoma) and oropharynx (oropharyngeal squamous cell carcinoma, OPSCC). Results: Despite the same etiology of these tumors, the composition and functionality of their lymphocytic infiltrate substantially differed. Cervical carcinoma displayed a 3-fold lower CD4:CD8 ratio and contained more activated CD8þCD103þCD161þ effector T cells and less CD4þCD161þ effector memory T cells than OPSCC. CD161þ effector cells produced the highest cytokine levels among tumor-specific T cells. Differences in CD4þ T-cell infiltration between cervical carcinoma and OPSCC were reflected in the detection rate of intratumoral HPV-specific CD4þ T cells and in their impact on OPSCC and cervical carcinoma survival. The peripheral blood mononuclear cell composition of these patients, however, was similar. Conclusions: The tissue of origin significantly affects the overall shape of the immune infiltrate in primary tumors.
UR - http://www.scopus.com/inward/record.url?scp=85059457688&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-18-1749
DO - 10.1158/1078-0432.CCR-18-1749
M3 - Article
C2 - 30224343
AN - SCOPUS:85059457688
SN - 1078-0432
VL - 25
SP - 240
EP - 252
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -