Prognostic impact of immune microenvironment in laryngeal and pharyngeal squamous cell carcinoma: Immune cell subtypes, immuno-suppressive pathways and clinicopathologic characteristics
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Georgia Karpathiou1, Francois Casteillo1, Jean-Baptiste Giroult2, Fabien Forest1, Pierre Fournel4, Alessandra Monaya1, Marios Froudarakis3, Jean Marc Dumollard1, Jean Michel Prades2, Michel Peoc'h1
1Department of Pathology, North Hospital, University Hospital of St-Etienne, St-Etienne, France
2Department of Head and Neck Surgery, North Hospital, University Hospital of St-Etienne, St-Etienne, France
3Department of Pneumonology, North Hospital, University Hospital of St-Etienne, St-Etienne, France
4Oncology Institute Lucien Neuwirth, St-Etienne, France
Georgia Karpathiou, email: [email protected]
Keywords: PD-L1, CTLA4, macrophages, dendritic cells
Received: July 15, 2016 Accepted: December 02, 2016 Published: December 27, 2016
Background: Immune system affects prognosis of various malignancies. Anti-immune pathways like PD-L1 and CTLA4 are used by the tumor to overcome immune system and they serve as immunotherapy targets. The immune microenvironment of head-and-neck squamous cell carcinoma (SCCHN) has not been sufficiently studied.
Patients and Methods: 152 SCCHN were immunohistochemically studied for the expression of CD3, CD8, CD57, CD4, granzyme b, CD20, CD163, S100, PD-L1, CTLA4 and CXCR4.
Results: CD3, CD8, CD57 and stromal S100 higher density is a good prognostic factor (p=0.02, 0.01, 0.02, 0.03 respectively). CTLA4 tumor expression is a poor prognostic factor (p=0.05). The rest immune cells do not affect prognosis. CD3 and CD8 density does not correlate with clinicopathological factors or p16/p53 expression, while CD57 and CD4 higher density is associated with the absence of distant metastases (p=0.03 and 0.07, respectively). Higher CD20 and S100 density is associated with lower T stage (p=0.04 and 0.03, respectively). PD-L1 expression is higher in CD3, CD8, and CD163 infiltrated tumors and in histologically more aggressive tumors. Response to neoadjuvant chemotherapy is better in highly CD3 infiltrated tumors and in tumors with less intraepithelial macrophages.
Conclusion: Rich T-lympocytic and dendritic cell response is a good prognostic factor in SCCHN, whereas tumors expressing CTLA4 show poor prognosis. PDL1 expression does not affect prognosis, but it is expressed in histologically more aggressive tumors and in T-cells rich tumors. Response to induction chemotherapy is better in tumors less infiltrated by macrophages and mostly infiltrated by T cells.
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