ICHNO-ECHNO 2022 - Abstract Book

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ICHNO-ECHNO 2022

control(LC), loco-regional control(LRC), disease free survival(DFS) were 36.1%, 48.3%, 35.8% & 27.4% respectively. Median laboratory values of the study population were taken as a cut off for further analysis. On Univariate analysis low NLR ( ≤ 2.8), PLR ( ≤ 143.5), High LMR (>3.6) and High PNI (>41) showed significant correlation with better OS, LC, LRC and DFS. On Multivariate analysis (MVA) high PNI was the strongest predictor for better LC (HR 0.78 95% CI 0.61-0.99, p 0.04), LRC (HR 0.75 95% CI 0.61-0.93, p 0.009), DFS (HR 0.73 95% CI 0.60-0.89, p 0.003) as well as OS (HR 0.64 95% CI 0.52-0.80, p <0.001) and low NLR was associated with better LC (HR 0.68 95% CI 0.51-0.92 p 0.013), LRC (HR 0.73 95% CI 0.56-0.95, p 0.02), DFS (HR 0.77 95% CI 0.56-0.96, p 0.04). Low PLR showed significant correlation on MVA only for better OS (HR 0.75 95% CI 0.58- 0.96, p 0.02) while LMR did not show any correlation on MVA for any of the outcomes. Conclusion Pre-treatment Immune inflammation biomarkers & PNI are prognostic predictors in OPSCC treated with RT. These markers can be used to develop prognostic model for predicting treatment outcomes, which can guide for selection of patients for intensifications or deintensification of treatment.

PO-0152 M2 as a therapeutic target in HNSCC: differentiation from THP-1 to M1 and M2a macrophage phenotypes

G. Descamps 1 , S. Furgiuele 2 , F. Journe 2 , S. Saussez 3

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 University of Mons, Laboratory of human anatomy and experimental oncology, Mons, Belgium Purpose or Objective Head and neck squamous cell carcinomas (HNSCCs) are aggressive tumours since they are associated with poor treatment responsiveness and poor prognosis, only 50% of patients are alive 5 years after diagnosis. The adaptive immune response plays a significant role in the tumorigenesis. In fact, immune cells are major components of the tumor microenvironment (TME), particularly, the tumour-associated macrophages (TAMs) which are involved in many tumorigenic steps. The macrophages are basically categorised into pro-inflammatory M1 versus anti-inflammatory M2, related to TAMs. The latter are an interesting target to fight cancer. A lot of strategies aimed to induce a switch to macrophage phenotype in order to produce an anti-tumoral TME. The methodology of macrophages polarization is highly controversial in the literature, so we would like to standardize this step. After all, we would like to apply this protocol to study the dual influence of these macrophages in HNSCCs cell lines and also in order to switch TAMs immunosuppressive in anti-tumor phenotype. Materials and Methods First, we carried out and validated a monocyte-to-macrophage polarization protocol to generate some macrophage subtypes (M0, M1 and M2). M0 were generated through exposure of THP1 monocytes to different concentrations (25 or 100 ng/ml) of phorbol 12-myristate-13 acetate (PMA) during 24h. Then, M0 were differentiated in M1 with lipopolysaccharides (LPS) and IFN- γ or in M2 with IL-4 and IL-13 human interleukins. The different phenotypes were confirmed by the identification of some characteristic markers by immunofluorescence (CD14, CD36, CD68, CD86, CD206, NRF2, NF- κ B), RTqPCR (CD68, CD80, SOCS1, SOCS3, IL-12, PD-L1, CCL2, CD206, KGA, SLC1A5, NOX2, SOD2, NRF2) and FACS (CD14, CD68, CD80, CD163, CD206). Moreover, we evaluate the stability of the different phenotypes over 72h. We would like to switch M2 phenotype to M1 by targeting metabolism using CB839 and ROS by using PRIMA- 1MET . We will also irradiate M2 with x-ray and expose them with Fe 2 O 3 nanoparticles. Results We demonstrated that the choice of PMA concentration has a critical impact on the molecular signature and the gene expression of the different subtypes induced. Indeed, the use of 25ng/ml concentration seems to be more appropriate than 100ng/ml to polarize monocyte to M1 macrophages. But, M2 phenotype seems to be more specific with higher concentration (100ng/ml). Polarized-macrophages, M1 and M2, seem to be stable in time. Conclusion With this study we highlight that appropriated polarization conditions are crucial to obtain some distinct immune cell lines for in vitro study. In the oncology field, targeting specifically these TAMs will be a promising therapeutic approach based on the continuum plasticity and flexibility between macrophages phenotypes.

PO-0153 Establishment of 3D co-culture model of head and neck squamous cell carcinomas and monocytes cells

G. Descamps 1 , N. Mhaidly 2 , F. Journe 2 , S. Saussez 2

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 Purpose or Objective Head and neck cancer remains one of the most challenging solid tumors to treat. Our fields of research are focused on immune alterations occurring during cancer progression, especially human papillomavirus (HPV)-related head and neck squamous cell carcinomas (HNSCCs). Most aggressive solid tumors have high levels of myeloid cell infiltration, namely tumor associated macrophages (TAM). TAM are a key component of the tumor microenvironment and have been shown to play an important role in the progression of cancer. Depending on the tumor environment stimuli, macrophages have two different phenotypes. M1 macrophages have anti-tumor effects and M2 macrophages have pro-tumor actions to create a favorable