TREM-1 expression in HPV-related oropharyngeal squamous cell carcinoma.

Abstract

e17545 Background: Immunotherapy in head and neck squamous cell carcinoma (SCC) is a hot topic and PD1/PDL-1 checkpoint blockade is a promising approach even if there is a lack of robust progno-stic/predictive biomarkers and treatment benefits in overall survival are variable. Triggering Receptor Expressed on Myeloid cell 1 (TREM-1) reverses the M2-polarizing effect of hypoxia imparting a M1-skewed pro-inflammatory phenotype to macrophages that controls tumour growth. Aim of this study is to evaluate the prognostic role of TREM-1 in oropharyngeal (OP) SCC. Methods: In 25 patients with stage III-IV HPV+ OPSCC we evaluated, with immunohistochemistry, in surgical specimens the following immunologic parameters in intratumoral (IT) and peritumoral (PT) environment: PD1-PDL-1 (1+ = < 20% positive cells (pc); 2+ = 21-50% pc; 3+ = > 50% pc) CD4, CD8, FOXP3 (1+ = < 10% pc; 2+ = 10-20% pc ; 3+ = > 20% pc) IL22 (1+ = 1-33% pc, 2+ = 34-67% pc, 3+ = > 67% pc) and TREM ( 1+ = 1-50% pc, 2+ = > 50% pc). The McNemar test was used to assess differences between IT and PT environment. Results: CD4 IT 0/1+ = 12% 2+/3+ = 88% PT 0/1+ = 6% 2+/3+ = 94% FOXP3 IT 0/1+ = 88% 2+/3+ = 12% PT 0/1+ = 65% 2+/3+ = 35% CD8 IT 0/1+ = 12% 2+/3+ = 88% PT 0/1+ = 48% 2+/3+ = 52% PD1 IT 0/1+ = 100% 2+/3+ = 0% PT 0/1+ = 100% 2+/3+ = 0% PDL1 IT 0/1+ = 53% 2+/3+ = 47% PT 0/1+ = 6% 2+/3+ = 94% IL22 IT 0/1+ = 59% 2+/3+ = 41% PT 0/1+ = 29% 2+/3+ = 71% TREM-1 IT 0/1+ = 94% 2 + = 6% PT 0/1+ = 82%* 2+ = 18% * 1+ = 64% Statistical analysis showed a concordant expression of CD4, CD8 and PDL-1 both in IT and PT while TREM-1 was more expressed in PT (p = .001) and PD-1 in IT (p = 0.12).There was no correlation between TREM-1 pc and CD68 and CD35 pc. Tumours with low PT TREM-1 positivity have a lowest risk of relapse (p = .01). Conclusions: HPV+ OPSCC is promoted by inflammatory infiltrate anergy. TREM-1 PT positivity has unfavourable impact on relapse.