563 - Expression of immune response biomarkers in head and neck squamous cell carcinoma (HNSCC) in irradiated area

Background

HNSCC occurring in previously irradiated area have a poor prognosis. With immunotherapy, the inhibition of negative regulators of immune checkpoints programmed cell death ligand-1 (PD-L1) and CD8+ tumor-infiltrating lymphocytes (TILs) have been of greatest importance for antitumor immune response. Yet, the immune landscape of pretreated area remains poorly documented and should be investigated, especially since locoregional recurrences have recently been described as a predominant site of hyperprogression. We aimed to assess the tumoral microenvironment in terms of biomarkers for tumor immune response in irradiated area compared to de novo tumors.

Methods

This retrospective monocentric study analyzed 100 HNSCC tumor tissues from patients who had undergone surgery between January 2010 and November 2017. We compared the immune microenvironment in 50 de novo tumors and 50 tumor recurrence occurring within irradiated area. Formalin-fixed and paraffin embedded tumor tissue samples were reviewed by an experimented pathologist for immunohistochemistry. We assessed p16 status, CD3+ and CD8+ TILs and PD-L1 expression on tumor and immune cells, in stromal and intratumoral components.

Results

The density of CD3+ TILs was significantly lower, whether in intratumoral or stromal region within irradiated areas (p = 0.003 and p = 0.020 respectively). The expression of CD8+ TILs was not significantly different between the two cohorts. The percentage of tumor cells expressing PD-L1 TC (TPS=1%) was significantly lower in tumours developed within irradiated area than in de novo tumors (56.0% vs 86.0%) (p < 0.001). Immune cells expressing PDL-1 were less frequent in tumors within irradiated areas. Predominant microenvironment type in irradiated area cohort was adaptative immune resistance.

Conclusions

There were persistence of cytotoxic cells and lower expression of PD-L1 and CD3+ TILs in tumors within irradiated area. This study provides first hypothesis to explain the fact that these lesions are less responsive to immunotherapy although they may still have antitumor capacity. The assessment of predictive biomarkers in patients treated by immunotherapy in randomized trials is required.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Dr Lionnel Geoffrois.

Funding

Has not received any funding.

Disclosure

C. Borel: Honoraria (self): Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS. L. Geoffrois: Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self): Ipsen; Honoraria (self): Novartis; Travel / Accommodation / Expenses: Merck Serono. All other authors have declared no conflicts of interest.