ICHNO-ECHNO 2022 - Abstract Book
S92
ICHNO-ECHNO 2022
PO-0147 Variation of T cells activation and PD-1 expression in sentinel node in oral SCC
K. Piersiala 1
1 Karolinska University Hospital , Otorhinolaryngology , Stockholm, Sweden
Purpose or Objective Improved understanding of the host's immune status in oral squamous cell carcinoma (OSCC) may facilitate identification of patients at higher risk of recurrence and improve patients' selection for ongoing clinical trials assessing the effectiveness of immune checkpoint inhibitors (ICI). ICI have revolutionized cancer management, yet the effect of systemic anti-PD-1 treatment is predominantly studied in tumor-infiltrating lymphocytes. Its impact on PD-1 expressing cells in tumor-draining lymph nodes (TDLNs) is not well understood and yet to be explored. Thus, further research aiming for better understanding of the PD-1 pathway not only in tumor tissue but also in TDLNs is warranted. In this project, we aimed to investigate Sentinel Node-derived T cells characteristics and their impact on survival. Materials and Methods We enrolled prospectively 20 OSCC patients treated at Karolinska University Hospital, Stockholm, Sweden with primary tumour excision and elective neck dissection. On top of the standard treatment, the enrolled patients underwent sentinel node procedure. T cells derived from Sentinel nodes, non-sentinel nodes, primary tumour and PBMC were analyzed in flow cytometry. Results Our data showed that both helper and cytotoxic T lymphocytes in OSCC tissue were highly activated and expressed high level of PD-1 (over 70% positivity). Lymphocytes in TDLNs and peripheral blood expressed significantly lower levels of PD-1 and other activation markers compared to TILs. Furthermore, we proved that patients with a high percentage of CD3+ PD- 1+ cells in TDLNs had significantly lower disease-free and overall survival rates (log-rank test P = .0272 and P = .0276, respectively). Sentinel nodes derived T regulatory cells were also significantly more activated compared with non-sentinel nodes. Conclusion Taken together, we proved that flow cytometry of lymph nodes in OSCC is feasible and may be used to investigate whether PD-1 levels in TDLNs correspond with survival and potentially with response to anti-PD-1 therapy. Such knowledge may ultimately help guide anti-PD-1 treatmen 1 University of Mons, Laboratory of human anatomy and experimental oncology, Mons , Belgium; 2 University of Mons, Laboratory of human anatomy and experimental oncology, Mons, Belgium; 3 Saint-Pierre Hospital, Department of Otolaryngology and Head and Neck Surgery, Brussels, Belgium Purpose or Objective Human papillomavirus infection is causally associated with the development of head and neck squamous cell carcinomas (HNSCCs), particularly in the oropharynx where p16 expression pattern is used as a surrogate marker of this infection. Because the reaction of the host immune system to these tumors remains biologically complex, this study focused on tumor- associated immunity in a series of HPV+ and HPV- HNSCCs from various anatomical sites and aimed to analyze the biological and prognostic implications of p16 status. Indeed, a better understanding of the immune context could allow to offer a personalized treatment and thus probably increase the survival of HNSCC patients. Materials and Methods p16 expression patterns and infiltrated immune cells were analyzed through immunohistochemistry of p16, CD1a, CD68, CD80, CD163, CD8, FoxP3 and PD-L1 on surgically resected HNSCCs (n=40). p16 immunoexpression was defined as positive when more than 70% of immune cells were labelled both in the nucleus and the cytoplasm. Each immune cell type was counted in intratumoral (IT) et stromal (ST) compartments. Optimal cut-offs were established to separate the population regarding to survival so that the prognostic value and the recurrence-free survival (RFS) were determined using Kaplan Meier curves and Cox regression models. Comparison of immune cell infiltration between two groups was evaluated using Mann-Whitney U test. Results First, we found that among the clinical variables only the p16 status was significantly correlated with the RFS. Regarding the prognostic value of immune cells, a high infiltration of FoxP3 in the stroma of HNSCC patients was associated with a longer RFS as well as a high recruitment of macrophages CD68+ in intratumoral increased the overall survival of these patients. Interestingly, we reported significant differences in immune cells recruitment between p16+ and p16- patients. Lymphocyte populations (CD8 and FoxP3) were significantly more abundant in p16+ tumors while Langerhans cells and the three phenotypes of macrophages (CD68, CD80, CD163) were less infiltrated. Conclusion In conclusion, p16+ patients exhibit an upregulated enrichment of T-lymphocytes along with a drastic decrease in macrophages and antigen-presenting cells. These findings suggest that p16 positivity is associated with a drop in the recruitment of cells linked to the innate immune system in parallel with a massive recruitment of lymphocyte cells which depend on the adaptive immune system. Such observation will have to be confirmed on an extent cohort. PO-0148 The immune landscape of HPV+ and HPV- head and neck cancers: a comparison of immune infiltration G. Descamps 1 , S. Furgiuele 2 , A. Yanni 3 , D. Dequanter 3 , F. Journe 1 , S. Saussez 1
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