Panagiota Economopoulou1, George Koutsodontis1, Areti Strati2, Efthymios Kirodimos3, Evangelos Giotakis4, Pavlos Maragoudakis5, Constantine Prikas5, Nikolaos Papadimitriou5, Christos Perisanidis6, Eleni Gagari7, Ioannis Kotsantis1, Elena Vagia1, Maria Anastasiou1, Maria Gkotzamanidou1, George Kavourakis1, Evi Lianidou2, Amanda Psyrri8. 1. Section of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, 1st Rimini St, 12462, Haidari, Athens, Greece. 2. Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli, Zografou 15772, Athens, Greece. 3. Department of Otolaryngology-Head and Neck Surgery, Hippokration General Hospital, University of Athens, 114 Vasilissis Sofias Ave, 11527 Athens, Greece. 4. Department of Otorhinolaryngology, Facial Plastic and Reconstructive Surgery, Städtisches Klinikum Karlsruhe, Moltkestraße 90, 76133 Karlsruhe, Germany. 5. 2nd Otolaryngology Department, Attikon University Hospital, 1st Rimini St, 12462, Haidari, Athens, Greece. 6. Department of Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria. 7. Oral Medicine Clinics, A. Syggros Hospital of Dermatologic and Venereal Diseases, Department of Dermatology, School of Medicine, University of Athens, Greece, 5th I. Dragoumi St, 16121 Athens, Greece. 8. Section of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, 1st Rimini St, 12462, Haidari, Athens, Greece. Electronic address: psyrri237@yahoo.com.
Abstract
OBJECTIVES: Chemoradiation can induce immunogenic (ICD) or tolerogenic cell death. ICD relies on the generation of damage-associated molecular patterns which can stimulate toll-like receptors (TLRs). We sought to determine whether we can predict responses to chemoradiation by measuring surrogate biomarkers of ICD in a cohort of patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: In a cohort of 113 LA HNSCC pts we evaluated expression of TLR4, TLR7 and TLR9 in the EpCAM + circulating tumor cell (CTC) fraction at baseline and after cisplatin chemoradiation. We also quantified changes in chemokines CXCL10, CXCL16 and IL-2R in the serum. RESULTS: Seventy three patients had evaluable specimens. Among cases with biomarker assessment at baseline and post treatment, 36.8% had an increase in CXCL10 levels (p = 0.022), 73.7% had an increase in CXCL16 levels (p = 0.002) and 63.8% had an increase in IL2Ra levels (p = 0.032) with treatment. 52.0% of evaluable cases at baseline and post-treatment had an increase in TLR4 levels (p = 0.996), 42.9% had an increase in TLR7 levels (p = 0.042) and 27.7% had increase in TLR9 levels (p = 0.011) with treatment. CXCL10 levels at baseline were significantly associated with PFS and OS (p = 0.010 and p = 0.032, respectively). CONCLUSIONS: Our results suggest that chemoradiation leads to quantifiable effects in surrogate markers of ICD. These effects may inform trials combining chemoradiation with immune checkpoint inhibitors. In addition, CXCL10 has prognostic effect in pts treated with chemoradiation.
OBJECTIVES: Chemoradiation can induce immunogenic (ICD) or tolerogenic cell death. ICD relies on the generation of damage-associated molecular patterns which can stimulate toll-like receptors (TLRs). We sought to determine whether we can predict responses to chemoradiation by measuring surrogate biomarkers of ICD in a cohort of patients with locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: In a cohort of 113 LA HNSCC pts we evaluated expression of TLR4, TLR7 and TLR9 in the EpCAM + circulating tumor cell (CTC) fraction at baseline and after cisplatin chemoradiation. We also quantified changes in chemokines CXCL10, CXCL16 and IL-2R in the serum. RESULTS: Seventy three patients had evaluable specimens. Among cases with biomarker assessment at baseline and post treatment, 36.8% had an increase in CXCL10 levels (p = 0.022), 73.7% had an increase in CXCL16 levels (p = 0.002) and 63.8% had an increase in IL2Ra levels (p = 0.032) with treatment. 52.0% of evaluable cases at baseline and post-treatment had an increase in TLR4 levels (p = 0.996), 42.9% had an increase in TLR7 levels (p = 0.042) and 27.7% had increase in TLR9 levels (p = 0.011) with treatment. CXCL10 levels at baseline were significantly associated with PFS and OS (p = 0.010 and p = 0.032, respectively). CONCLUSIONS: Our results suggest that chemoradiation leads to quantifiable effects in surrogate markers of ICD. These effects may inform trials combining chemoradiation with immune checkpoint inhibitors. In addition, CXCL10 has prognostic effect in pts treated with chemoradiation.
Authors: Alexios-Fotios A Mentis; Petros D Grivas; Efthimios Dardiotis; Nicholas A Romas; Athanasios G Papavassiliou Journal: Cell Mol Life Sci Date: 2020-04-24 Impact factor: 9.261
Authors: Hager Mohamed; Rita A Esposito; Michele A Kutzler; Brian Wigdahl; Fred C Krebs; Vandana Miller Journal: Plasma Process Polym Date: 2020-07-13 Impact factor: 3.877
Authors: Panagiota Economopoulou; Athina Kladi-Skandali; Areti Strati; George Koytsodontis; Efthymios Kirodimos; Evangelos Giotakis; Pavlos Maragoudakis; Eleni Gagari; Eirini Maratou; George Dimitriadis; Ioannis Kotsantis; Elena Vagia; Maria Anastasiou; Maria Gkotzamanidou; George Kavourakis; Evi Lianidou; Amanda Psyrri Journal: ESMO Open Date: 2020-05
Authors: Karl Payne; Matthew Pugh; Jill Brooks; Nikolaos Batis; Graham Taylor; Paul Nankivell; Hisham Mehanna Journal: Int J Mol Sci Date: 2020-11-03 Impact factor: 6.208