Abstract Book

S873

ESTRO 37

EP-1622 Irradiation alters PD-L1 expression in RCC cell lines via IFN-gamma independent pathways. Q. Tang 1 , S. Lie 2 , P. Guan 1 , B.T. Teh 1 , K.W. Yeoh 2 1 National Cancer Center Singapore, Medical Sciences, Singapore, Singapore 2 National Cancer Center Singapore, Radiation Oncology, Singapore, Singapore Purpose or Objective The immune checkpoint target PD-1 has reinvigorated the interest for Renal Cell Carcinoma (RCC) treatment in the field of immunotherapy. Yet, its success has been limited by suboptimal response rates due to acquired resistance employed by tumour cells via mechanisms not yet identified. Radiation therapy which is a modality used in over 50% of all cancer patients is mostly reserved for palliative settings in RCC. Interestingly, it has been shown to have immunomodulatory effects to enhance the efficacy of immunotherapy for unresponsive tumours. In this study, we aim at investigating how radiation affects PD-L1 and cytokines in RCC tumour cells after radiation. Material and Methods We employed ATP cell viability assay to determine the survival and growth rate of two RCC cell lines when subjected to irradiation. We also established radiated RCC cell lines through one-dose treatment and the surviving cells was measured and collected through clonogenic assay. To study the PD-L1 expression as the basis of our study, we employed quantitative PCR, Flow cytometry and immunoblotting. Cellular signalling pathway was measured via immunoblotting and the cytokine productions was measured using Luminex Multiplex assay as well as ELISA. Results Our study showed that radiation therapy may have immunomodulatory effects for RCC cell lines by regulating PD-L1 expression through mechanisms other than the canonical IFN-γ activation. The analysis on cytokine and gene enrichment study suggested that the PD-L1 response may be regulated through inflammatory cytokines and chemokines-related pathways

Taken together, the strategy of combining radiotherapy and immunotherapy has the potential to improve the response rates of immunotherapy for patients with RCC.

Electronic Poster: Clinical track: Skin cancer / malignant melanoma

EP-1623 Overall survival of patients with cutaneous SCC metastasis to the axilla or groin N. Bucknell 1 , M. Bressel 2 , A. Webb 3 , D. Gyorki 3 , M. Henderson 3 , V. Estall 1 , A. Tiong 1 1 Peter MacCallum Cancer Center, Radiation Oncology, Melbourne, Australia 2 Peter MacCallum Cancer Center, Biostatistics and Clinical Trials Unit, Melbourne, Australia 3 Peter MacCallum Cancer Center, Surgical Oncology, Melbourne, Australia Purpose or Objective Metastasis of cutaneous squamous cell carcinoma (cSCC) to regional lymph nodes of the upper and lower limb are uncommon events. They are described in regions where there is high ultraviolet light exposure with populations of low Fitzpatrick score skin types. These cancers are generally treated with lymphadenectomy and adjuvant (chemo)radiotherapy for those with high risk features (tumours larger than 3cm, involvement of three or more nodes or extra-nodal extension). Unfortunately there is scant published data in this area to guide management: the largest retrospective series has 26 patients. We therefore examined a larger series of patients treated at our institution for their overall survival and prognostic factors. Material and Methods We performed a retrospective chart review of patients treated at our institution from January 2000 to July 2015. Included patients had histologically confirmed cSCC metastatic to either axilla or inguinal nodes, 18 years or older, did not have non-cutaneous primary identified and were treated with lymphadenectomy with/without adjuvant treatment. Overall survival (OS) was described using Kaplan-Meier methods and prognostic factors for OS were analysed with univariate Cox models. Results 78 patients met the inclusion criteria. The mean age was 73 years (29-95), 54 (67.9%) were male, 56 (72%) were ECOG 0 or 1 and 8 (10.5%) were immunosuppressed. Staging was performed with CT scan in 75 (96%) and PET in 39 (50%). 64 (82%) patients had axillary involvement while 14 (18%) involved the inguinal region. The average number of nodes involved was 3.7 (range: 1-22) and the mean size of the largest node was 47.9mm (range: 8-135). 63 (80.8%) had extra-nodal extension. Management was lymphadenectomy alone in 21 (27%) patients, lymphadenectomy and adjuvant radiotherapy in 54 (69.2%), lymphadenectomy and adjuvant chemo- radiotherapy 1 (1.3%) and neo-adjuvant radiotherapy followed by lymphadenectomy 2 (2.6%). 5 year OS was 33% (95% CI: 23-47%) in this population (figure). 31 (39.7%) recurred within the treated regional lymph nodes and 21 (26.9%) developed distant metastasis. On univariate analysis, significant factors for improved survival were younger age (p=0.016), better performance status (p=0.03), lack of immunosuppression (p=0.001), a lower lymphocyte ratio (p=0.015) and the use of radiotherapy (p=0.009).

Figure 1.Expression of PD-L1 Through Flow cytometry and qPCR

Figure 2. Radiation effect on secretions of cytokines using ELISA. Conclusion In our study, we demonstrated that radiation alters the immune profile of RCC cell lines by altering PD-L1 levels, cytokine secretion and immune-related gene expression.