Nadège Kindt1, Géraldine Descamps1, Imelda Seminerio1, Justine Bellier1, Jérôme R Lechien1, Quentin Mat1, Charles Pottier2, Philippe Delvenne2, Fabrice Journé3, Sven Saussez4. 1. Department of Human Anatomy and Experimental Oncology, Research Institute for Health Sciences and Technology, Faculty of Medicine and Pharmacy, University of Mons, 6 Ave du Champ de Mars, B-7000 Mons, Belgium. 2. Department of Pathology, C.H.U. - SART TILMAN, University of Liège, 4000 Liège, Belgium. 3. Department of Human Anatomy and Experimental Oncology, Research Institute for Health Sciences and Technology, Faculty of Medicine and Pharmacy, University of Mons, 6 Ave du Champ de Mars, B-7000 Mons, Belgium; Laboratory of Oncology and Experimental Surgery, Jules Bordet Institute, Université Libre de Bruxelles, 1000 Brussels, Belgium. 4. Department of Human Anatomy and Experimental Oncology, Research Institute for Health Sciences and Technology, Faculty of Medicine and Pharmacy, University of Mons, 6 Ave du Champ de Mars, B-7000 Mons, Belgium; Department of Oto-Rhino-Laryngology, Faculty of Medicine, Free University of Brussels (ULB), CHU St-Pierre, Rue Haute, 322, B-1000 Brussels, Belgium. Electronic address: sven.saussez@umons.ac.be.
Abstract
OBJECTIVES: Head and neck squamous cell carcinomas (HNSCC), one of the most frequent cancers in the world, are largely infiltrated by inflammatory immune cells. Our aim was to evaluate the number of Foxp3+ T cells in HNSCC, reporting its prognostic power in comparison to other risk factors. MATERIAL AND METHODS: Our clinical series was composed of 21 tumor-free peri-tumoral epithelia, 49 low grade dysplasia, 43 high grade dysplasia and 110 carcinoma samples including some cases with HPV infection. In vivo experiments were conducted on 80 C3H/HeN mice which were orthotopically injected with SCCVII CT, E7, E6 and E6/E7 cell lines. RESULTS: Foxp3+ T cell infiltration increased with tumor progression from normal epithelia, dysplasia to carcinoma and the increase is more important in HPV+ patients than in negative ones. Animal experiments revealed that E7 oncoprotein expression was significantly associated with an increase in Foxp3+ T cell recruitment in tumor, a delay in tumor onset and improved animal survival. Univariate Cox regression analyses demonstrated that high Foxp3+ T cell number in stromal compartment is associated with longer patient recurrence-free and overall survivals. Foxp3+ T cell number improved the prognostic value of tumor stage. Multivariate analyses reported that stromal Foxp3+ T cell number is a strong prognostic factor independent of classical risk factors such as tobacco, alcohol, and HPV status. CONCLUSION: Foxp3+ T cell number is a significant prognostic factor for HNSCC, improving the tumor stage, and that viral E7 may play a role in the Foxp3+ T cell infiltration to the tumor.
OBJECTIVES: Head and neck squamous cell carcinomas (HNSCC), one of the most frequent cancers in the world, are largely infiltrated by inflammatory immune cells. Our aim was to evaluate the number of Foxp3+ T cells in HNSCC, reporting its prognostic power in comparison to other risk factors. MATERIAL AND METHODS: Our clinical series was composed of 21 tumor-free peri-tumoral epithelia, 49 low grade dysplasia, 43 high grade dysplasia and 110 carcinoma samples including some cases with HPV infection. In vivo experiments were conducted on 80 C3H/HeN mice which were orthotopically injected with SCCVII CT, E7, E6 and E6/E7 cell lines. RESULTS:Foxp3+ T cell infiltration increased with tumor progression from normal epithelia, dysplasia to carcinoma and the increase is more important in HPV+ patients than in negative ones. Animal experiments revealed that E7 oncoprotein expression was significantly associated with an increase in Foxp3+ T cell recruitment in tumor, a delay in tumor onset and improved animal survival. Univariate Cox regression analyses demonstrated that high Foxp3+ T cell number in stromal compartment is associated with longer patient recurrence-free and overall survivals. Foxp3+ T cell number improved the prognostic value of tumor stage. Multivariate analyses reported that stromal Foxp3+ T cell number is a strong prognostic factor independent of classical risk factors such as tobacco, alcohol, and HPV status. CONCLUSION:Foxp3+ T cell number is a significant prognostic factor for HNSCC, improving the tumor stage, and that viral E7 may play a role in the Foxp3+ T cell infiltration to the tumor.
Authors: Ajaz A Bhat; Parvaiz Yousuf; Nissar A Wani; Arshi Rizwan; Shyam S Chauhan; Mushtaq A Siddiqi; Davide Bedognetti; Wael El-Rifai; Michael P Frenneaux; Surinder K Batra; Mohammad Haris; Muzafar A Macha Journal: Signal Transduct Target Ther Date: 2021-01-12
Authors: Thomas Brouwer; Marieke Ijsselsteijn; Jan Oosting; Dina Ruano; Manon van der Ploeg; Frederike Dijk; Bert Bonsing; Arantza Fariña; Hans Morreau; Alexander Vahrmeijer; Noel de Miranda Journal: Cancers (Basel) Date: 2022-08-10 Impact factor: 6.575