TY - JOUR
T1 - Tonsillar cancer with high cd8+ t‐cell infiltration features increased levels of dendritic cells and transcriptional regulation associated with an inflamed tumor microenvironment
AU - Jimenez, David Gomez
AU - Sobti, Aastha
AU - Askmyr, David
AU - Sakellariou, Christina
AU - Santos, Sofia Carreira
AU - Swoboda, Sabine
AU - Forslund, Ola
AU - Greiff, Lennart
AU - Lindstedt, Malin
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - Human papillomavirus (HPV) is the main causal agent of tonsillar cancer (TC) and HPV+ TC has a favorable prognosis compared to HPV– disease. In this study, we examined aspects of the tumor microenvironment of TC, focusing on T‐cells, dendritic cells (DC), and macrophages. Fresh biopsies of TC and the contralateral healthy tonsil (HT) were obtained from 20 patients, analyzed by multiparameter flow cytometry, and assessed against a detailed HPV‐status. Additionally, RNA-sequencing data from 38 TC samples available in the public database, The Cancer Genome Atlas (TCGA), were explored, focusing on the same leukocyte populations. HPV+ TC featured increased levels of CD8+ T‐cells and antigen‐presenting cells (cf. HPV– TC and HT, respectively). In HPV+ TC, CD8+ T‐cell frequencies correlated to DC levels independently of tumor stage, HPV 16 copy number, and E7 oncogene expression as well as frequencies of other leukocytes. Similarly, RNA sequencing data were explored by dividing the HPV+ TCs according to predefined CD8+ T‐cell scores in silico. Higher levels of genes expressed by antigen‐presenting cells and effector T‐cells, such as immune checkpoints and cytokines, were detected in the CD8HIGH HPV+ TC samples (cf. CD8LOW HPV+ TC). In conclusion, CD8HIGH HPV+ TC displays a unique inflammatory profile associated with increased effector T‐cell functions and the presence of antigen‐presenting cells in the tumor microenviron-ment. Further studies are warranted to assess if this information can be used on an individual basis to aid in prognosis and treatment decisions.
AB - Human papillomavirus (HPV) is the main causal agent of tonsillar cancer (TC) and HPV+ TC has a favorable prognosis compared to HPV– disease. In this study, we examined aspects of the tumor microenvironment of TC, focusing on T‐cells, dendritic cells (DC), and macrophages. Fresh biopsies of TC and the contralateral healthy tonsil (HT) were obtained from 20 patients, analyzed by multiparameter flow cytometry, and assessed against a detailed HPV‐status. Additionally, RNA-sequencing data from 38 TC samples available in the public database, The Cancer Genome Atlas (TCGA), were explored, focusing on the same leukocyte populations. HPV+ TC featured increased levels of CD8+ T‐cells and antigen‐presenting cells (cf. HPV– TC and HT, respectively). In HPV+ TC, CD8+ T‐cell frequencies correlated to DC levels independently of tumor stage, HPV 16 copy number, and E7 oncogene expression as well as frequencies of other leukocytes. Similarly, RNA sequencing data were explored by dividing the HPV+ TCs according to predefined CD8+ T‐cell scores in silico. Higher levels of genes expressed by antigen‐presenting cells and effector T‐cells, such as immune checkpoints and cytokines, were detected in the CD8HIGH HPV+ TC samples (cf. CD8LOW HPV+ TC). In conclusion, CD8HIGH HPV+ TC displays a unique inflammatory profile associated with increased effector T‐cell functions and the presence of antigen‐presenting cells in the tumor microenviron-ment. Further studies are warranted to assess if this information can be used on an individual basis to aid in prognosis and treatment decisions.
KW - CD8 T‐cells
KW - Dendritic cells
KW - Human papillomavirus
KW - Macrophages
KW - Tonsillar cancer
KW - Tumor microenvironment
U2 - 10.3390/cancers13215341
DO - 10.3390/cancers13215341
M3 - Article
C2 - 34771506
AN - SCOPUS:85117591529
VL - 13
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 21
M1 - 5341
ER -