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P2.03b-089 CD1C in Lung Adenocarcinoma: Prognosis and Cellular Origin
S990
IV tracer Ga68-RGD and measurements at three time points (30, 60 and 120 mins) prior treatment start and after completing 2 therapy cycles. Results: Mean age at diagnosis was 58.7±11.4 years. Of the 38 patients, 31 had complete data for analysis. After 2 treatment cycles, the PET-CT assessment response, based on baseline Lung/Spleen SUVmax index, showed an ORR of 7.9% and DCR of 47.3%. Median PFS of 3.7 months and median Hypertensive patients were more likely to have a higher PFS (6.3 vs. 3.3 months; p¼0.023), as well as patients with a larger baseline tumoral-volume by Ga68-RGD PET-CT (2.1 vs. 6.1 months; p¼0.007). Global OS was of 8.8 months. Nonsmokers were more likely to have larger OS (9.3 vs 4.2; p¼0.008). Also a median OS was longer among patients with higher Lung/Spleen SUVmax index percentage change after treatment (9.4 vs. 4.9 months; p¼0.05) was found. Conclusion: A larger baseline tumoral-volume can be associated to a higher progression-free survival due to the major cellular component to target with antiangiogenic therapy, as well as a strong association of larger survival assessed by the Lung/Spleen SUVmax index after treatment, marked by the Ga68-RGD radiotracer. Keywords: aVb3 integrin, Lung/Spleen SUVmax index, antiangiogenic therapy, Ga68-RGD PET-CT
P2.03b-089 CD1C in Lung Adenocarcinoma: Prognosis and Cellular Origin Topic: Biomarkers Chang-Qi Zhu,1 Michael Cabanero,1 Dalam Ly,1 Mamatjan Yasin,1 Kenneth Aldape,1 Frances Shepherd,2 Li Zhang,1 Ming Tsao3 1 Department of Laboratory Medicine and Pathobiology, University Health Network, Toronto/Canada, 2Dept of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto/ON/Canada, 3Departments of Pathology, Princess Margaret Cancer Centre and University of Toronto, Toronto/Canada Background: Adaptive immune response is critical for cancer surveillance and elimination. Dendritic cells (DC) arise from a hematopoietic lineage distinct from other leukocytes which play a central role in adaptive immunity. CD1C is expressed in DC, presenting exogenous lipid antigens to T cell receptor to activate “unconventional” T cells. This study aims to
Journal of Thoracic Oncology
Vol. 12 No. 1S
evaluate the cellular expression and prognostic value of CD1C. Methods: The study used 5 gene expression datasets: UHN181 [lung adenocarcinoma (ADC, n¼128), squamous cell carcinoma (SqCC, n¼43)], GSE30219 (ADC n¼81, non-ADC n¼138)], and 3 integrated cohorts [non-SqCC NSCLC (n¼1106), PRECOG (39 types of cancer, n¼w18,000), and TCGA (33 types of cancer, n¼11,000)]. Cancer Cell Line Encyclopedia (CCLE) data were used to determine if CD1C was expressed by cancer cell lines. CIBERSORT algorithm was used to estimate immune cell fraction and Cox proportional model was used to evaluate the association of CD1C expression with survival. Immunohistochemistry (IHC) was used to measure protein expression of CD1C. Results: Except for hematopoietic and lymphoid cancer cell lines, all CCLE cell lines lack CD1C expression. CIBERSORT analysis together with Pearson correlation analyses on the ADC cases in UHN181, the integrated cohort, and GSE30219 showed that CD1C was expressed by DC. IHC showed staining with a dendritic cell shape pattern. However, the staining of CD1C did not overlapped with CD11c staining, suggesting a specific DC subtype. Cox proportional regression revealed that CD1C was significantly prognostic in the UHN181 ADC cohort (HR¼0.75, p¼0.05) as the training set. When CD1C expression was categorized into 3 equal groups, the risk of death was reduced in high compared to low CD1C expression group (HR¼0.55, 95%CI 0.28-1.07, p¼0.07). CD1C is protective only in PD-L1 low expression group (n¼108, HR¼0.37, 95%CI 0.15-0.89, p¼0.026). The favorable prognosis associated with CD1C expression was validated in the integrated cohort of non-SqCC NSCLC (HR¼0.55, 95% CI 0.43-0.72, p<0.0001), and in GSE30219 ADC cohort (HR¼0.30, 95% CI 0.11-0.84, p¼0.02). In PRECOG and TCGA datasets, high CD1C expression is significantly good prognostic in all cancer types (p<110-7 and p<0.001, respectively), suggesting a universal protective role of CD1C expression in cancers. CD1C IHC score was highly correlated with CD1C mRNA expression in ADC patients of UHN181 and was prognostic (HR¼0.46, 95% CI 0.22-0.96, p¼0.039). Conclusion: CD1C preferentially is expressed on a subset of DCs and higher expression of CD1C is significant protective factor in all cancer types, especially in lung adenocarcinoma. Keywords: adaptive immunity, CD1C, lung adenocarcinoma, Prognosis
IV tracer Ga68-RGD and measurements at three time points (30, 60 and 120 mins) prior treatment start and after completing 2 therapy cycles. Results: Mean age at diagnosis was 58.7±11.4 years. Of the 38 patients, 31 had complete data for analysis. After 2 treatment cycles, the PET-CT assessment response, based on baseline Lung/Spleen SUVmax index, showed an ORR of 7.9% and DCR of 47.3%. Median PFS of 3.7 months and median Hypertensive patients were more likely to have a higher PFS (6.3 vs. 3.3 months; p¼0.023), as well as patients with a larger baseline tumoral-volume by Ga68-RGD PET-CT (2.1 vs. 6.1 months; p¼0.007). Global OS was of 8.8 months. Nonsmokers were more likely to have larger OS (9.3 vs 4.2; p¼0.008). Also a median OS was longer among patients with higher Lung/Spleen SUVmax index percentage change after treatment (9.4 vs. 4.9 months; p¼0.05) was found. Conclusion: A larger baseline tumoral-volume can be associated to a higher progression-free survival due to the major cellular component to target with antiangiogenic therapy, as well as a strong association of larger survival assessed by the Lung/Spleen SUVmax index after treatment, marked by the Ga68-RGD radiotracer. Keywords: aVb3 integrin, Lung/Spleen SUVmax index, antiangiogenic therapy, Ga68-RGD PET-CT
P2.03b-089 CD1C in Lung Adenocarcinoma: Prognosis and Cellular Origin Topic: Biomarkers Chang-Qi Zhu,1 Michael Cabanero,1 Dalam Ly,1 Mamatjan Yasin,1 Kenneth Aldape,1 Frances Shepherd,2 Li Zhang,1 Ming Tsao3 1 Department of Laboratory Medicine and Pathobiology, University Health Network, Toronto/Canada, 2Dept of Medical Oncology and Haematology, Princess Margaret Cancer Centre, Toronto/ON/Canada, 3Departments of Pathology, Princess Margaret Cancer Centre and University of Toronto, Toronto/Canada Background: Adaptive immune response is critical for cancer surveillance and elimination. Dendritic cells (DC) arise from a hematopoietic lineage distinct from other leukocytes which play a central role in adaptive immunity. CD1C is expressed in DC, presenting exogenous lipid antigens to T cell receptor to activate “unconventional” T cells. This study aims to
Journal of Thoracic Oncology
Vol. 12 No. 1S
evaluate the cellular expression and prognostic value of CD1C. Methods: The study used 5 gene expression datasets: UHN181 [lung adenocarcinoma (ADC, n¼128), squamous cell carcinoma (SqCC, n¼43)], GSE30219 (ADC n¼81, non-ADC n¼138)], and 3 integrated cohorts [non-SqCC NSCLC (n¼1106), PRECOG (39 types of cancer, n¼w18,000), and TCGA (33 types of cancer, n¼11,000)]. Cancer Cell Line Encyclopedia (CCLE) data were used to determine if CD1C was expressed by cancer cell lines. CIBERSORT algorithm was used to estimate immune cell fraction and Cox proportional model was used to evaluate the association of CD1C expression with survival. Immunohistochemistry (IHC) was used to measure protein expression of CD1C. Results: Except for hematopoietic and lymphoid cancer cell lines, all CCLE cell lines lack CD1C expression. CIBERSORT analysis together with Pearson correlation analyses on the ADC cases in UHN181, the integrated cohort, and GSE30219 showed that CD1C was expressed by DC. IHC showed staining with a dendritic cell shape pattern. However, the staining of CD1C did not overlapped with CD11c staining, suggesting a specific DC subtype. Cox proportional regression revealed that CD1C was significantly prognostic in the UHN181 ADC cohort (HR¼0.75, p¼0.05) as the training set. When CD1C expression was categorized into 3 equal groups, the risk of death was reduced in high compared to low CD1C expression group (HR¼0.55, 95%CI 0.28-1.07, p¼0.07). CD1C is protective only in PD-L1 low expression group (n¼108, HR¼0.37, 95%CI 0.15-0.89, p¼0.026). The favorable prognosis associated with CD1C expression was validated in the integrated cohort of non-SqCC NSCLC (HR¼0.55, 95% CI 0.43-0.72, p<0.0001), and in GSE30219 ADC cohort (HR¼0.30, 95% CI 0.11-0.84, p¼0.02). In PRECOG and TCGA datasets, high CD1C expression is significantly good prognostic in all cancer types (p<110-7 and p<0.001, respectively), suggesting a universal protective role of CD1C expression in cancers. CD1C IHC score was highly correlated with CD1C mRNA expression in ADC patients of UHN181 and was prognostic (HR¼0.46, 95% CI 0.22-0.96, p¼0.039). Conclusion: CD1C preferentially is expressed on a subset of DCs and higher expression of CD1C is significant protective factor in all cancer types, especially in lung adenocarcinoma. Keywords: adaptive immunity, CD1C, lung adenocarcinoma, Prognosis