Journal Article
. 2012 Jun; 7(6):e38711.
doi: 10.1371/journal.pone.0038711.

Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer

Anders Näsman 1 Mircea Romanitan  Cecilia Nordfors  Nathalie Grün  Hemming Johansson  Lalle Hammarstedt  Linda Marklund  Eva Munck-Wikland  Tina Dalianis  Torbjörn Ramqvist  
  • PMID: 22701698
  •     35 References
  •     81 citations


Background: Human papillomavirus (HPV) is a causative factor for tonsillar squamous cell carcinoma (TSCC) and patients with HPV positive (HPV(+)) TSCC have a better clinical outcome than those with HPV negative (HPV(-)) TSCC. However, since not all patients with HPV(+) TSCC respond to treatment, additional biomarkers are needed together with HPV status to better predict response to therapy and to individualize treatment. For this purpose, we examined whether the number of tumor infiltrating cytotoxic and regulatory T-cells in TSCC correlated to HPV status and to clinical outcome.

Methods: Formalin fixed paraffin embedded TSCC, previously analysed for HPV DNA, derived from 83 patients, were divided into four groups depending on the HPV status of the tumor and clinical outcome. Tumors were stained by immunohistochemistry and evaluated for the number of infiltrating cytotoxic (CD8(+)) and regulatory (Foxp3(+)) T-cells.

Results: A high CD8(+) T-cell infiltration was significantly positively correlated to a good clinical outcome in both patients with HPV(+) and HPV(-) TSCC patients. Similarly, a high CD8(+)/Foxp3(+) TIL ratio was correlated to a 3-year disease free survival. Furthermore, HPV(+) TSCC had in comparison to HPV(-) TSCC, higher numbers of infiltrating CD8(+) and Foxp3(+) T-cells.

Conclusions: In conclusion, a positive correlation between a high number of infiltrating CD8(+) cells and clinical outcome indicates that CD8(+) cells may contribute to a beneficial clinical outcome in TSCC patients, and may potentially serve as a biomarker. Likewise, the CD8(+)/Foxp3(+)cell ratio can potentially be used for the same purpose.

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Immunodiagnosis and Immunotherapeutics Based on Human Papillomavirus for HPV-Induced Cancers.
Zhen Dong, Renjian Hu, +6 authors, Hongjuan Cui.
Front Immunol, 2021 Jan 26; 11. PMID: 33488587    Free PMC article.
Prediction of Response in Head and Neck Tumor: Focus on Main Hot Topics in Research.
Liliana Belgioia, Silvia Daniela Morbelli, Renzo Corvò.
Front Oncol, 2021 Jan 26; 10. PMID: 33489911    Free PMC article.
Single-Cell Deconvolution of Head and Neck Squamous Cell Carcinoma.
Zongtai Qi, Yating Liu, +12 authors, Sidharth V Puram.
Cancers (Basel), 2021 Apr 04; 13(6). PMID: 33799782    Free PMC article.
Immuno-Oncological Biomarkers for Squamous Cell Cancer of the Head and Neck: Current State of the Art and Future Perspectives.
Stijn J De Keukeleire, Tijl Vermassen, +3 authors, Sylvie Rottey.
Cancers (Basel), 2021 May 01; 13(7). PMID: 33916646    Free PMC article.
Targeted Therapy With PI3K and FGFR Inhibitors on Human Papillomavirus Positive and Negative Tonsillar and Base of Tongue Cancer Lines With and Without Corresponding Mutations.
Stefan Holzhauser, Nicole Wild, +5 authors, Tina Dalianis.
Front Oncol, 2021 May 29; 11. PMID: 34046344    Free PMC article.
Development of Exhaustion and Acquisition of Regulatory Function by Infiltrating CD8+CD28- T Lymphocytes Dictate Clinical Outcome in Head and Neck Cancer.
Daniela Fenoglio, Liliana Belgioia, +18 authors, Gilberto Filaci.
Cancers (Basel), 2021 Jun 03; 13(9). PMID: 34066538    Free PMC article.
Prognostic Potential of Tumor-Infiltrating Immune Cells in Resectable Oral Squamous Cell Carcinoma.
Ana Caruntu, Liliana Moraru, +7 authors, Sabina Zurac.
Cancers (Basel), 2021 Jun 03; 13(9). PMID: 34066837    Free PMC article.
Prognostic Markers and Driver Genes and Options for Targeted Therapy in Human-Papillomavirus-Positive Tonsillar and Base-of-Tongue Squamous Cell Carcinoma.
Anders Näsman, Stefan Holzhauser, +4 authors, Tina Dalianis.
Viruses, 2021 Jun 03; 13(5). PMID: 34069114    Free PMC article.
Statin use and head and neck squamous cell carcinoma outcomes.
Kayla R Getz, Emily Bellile, +6 authors, Alison M Mondul.
Int J Cancer, 2020 Dec 16;. PMID: 33320960    Free PMC article.
Oropharyngeal Squamous Cell Carcinoma Treatment in the Era of Immune Checkpoint Inhibitors.
Peter L Stern, Tina Dalianis.
Viruses, 2021 Jul 03; 13(7). PMID: 34202255    Free PMC article.
Immunotherapy Advances in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Its Relationship With Human Papillomavirus.
Huanhuan Wang, Qin Zhao, +7 authors, Xin Jiang.
Front Immunol, 2021 Jul 27; 12. PMID: 34305889    Free PMC article.
Systematic Review.
Tumor Immunity and Immunotherapy for HPV-Related Cancers.
Achraf A Shamseddine, Bharat Burman, +2 authors, Nadeem Riaz.
Cancer Discov, 2021 May 16; 11(8). PMID: 33990345    Free PMC article.
Human Papillomavirus and Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region: A Comprehensive Review on Clinical Implications.
Mikkel Hjordt Holm Larsen, Hani Ibrahim Channir, Christian von Buchwald.
Viruses, 2021 Aug 11; 13(7). PMID: 34372502    Free PMC article.
Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results.
Renata Ferrarotto, Diana Bell, +16 authors, Neil D Gross.
Clin Cancer Res, 2020 Apr 10; 26(13). PMID: 32269052    Free PMC article.
Assessment of Immune Cell Populations in Tumor Tissue and Peripheral Blood Samples from Head and Neck Squamous Cell Carcinoma Patients.
Ana Caruntu, Liliana Moraru, +6 authors, Monica Neagu.
Anal Cell Pathol (Amst), 2021 Oct 26; 2021. PMID: 34692375    Free PMC article.
Exploring the roles of HPV16 variants in head and neck squamous cell carcinoma: current challenges and opportunities.
Daniela Cochicho, Rui Gil da Costa, Ana Felix.
Virol J, 2021 Nov 10; 18(1). PMID: 34749746    Free PMC article.
Tonsillar Cancer with High CD8+ T-Cell Infiltration Features Increased Levels of Dendritic Cells and Transcriptional Regulation Associated with an Inflamed Tumor Microenvironment.
David Gomez Jimenez, Aastha Sobti, +6 authors, Malin Lindstedt.
Cancers (Basel), 2021 Nov 14; 13(21). PMID: 34771506    Free PMC article.