1178P Integrated pathological analysis to develop a Gal-9 based immune survival stratification to predict the outcome of lung large cell neuroendocrine carcinoma

Abstract

For large cell neuroendocrine lung carcinoma (LCNEC) therapy, immunotherapy might have unique advantage. The role of Gal-9 in LCNEC remains incompletely understood. Computer-extracted feature in pathology images may reflect immune infiltration. This study aimed to integrate pathological characteristics to develop a Gal-9 based immune risk score in the LCNEC. By mean of IHC, the expression of Gal-9 and other immune markers on both tumor cells and TILs in 122 surgical LCNEC samples were evaluated. The Gal-9 based immune risk model was built and the prognostic performance was evaluated. Then, the effects of Gal-9 and immune risk model on LCNEC immune infiltration were studied in GEO, validated in our cohort by Histology-based Digital-Staining which evaluated the immune cell proportion and image characteristics. In the LCNEC cohort for IHC, 43 (35.2%) were positive Gal-9 expression on tumor cells. The high Gal-9 protein expression on tumor cells indicated worse overall survival (P=0.029, HR=1.83, 95CI: 1.01-3.31). The immune risk model which consisted of Gal-9 on tumor cells, CD3, CD4, PD-L1 on tumor cells and PD-1was constructed and validated to discriminate high or low-risk LCNEC patients. The prognostic predictive performance of immune risk model was good with AUC of 1, 3, 5 years survival: 0.808, 0.763, 0.787 in whole cohort. High Gal-9 related enrichment pathways in LCNEC involved immune suppression and immune tolerance. The high-risk group demonstrated an immune-desert tumor filled with less T cells but more neutrophils (P=0.041). HD-staining pathology results from a total of 108369 cells validated that high-risk group has less stroma cells (13.9% vs 11.1%), but more tumor cells (63.9%% vs 59.6%), meanwhile, revealed that high-risk group has the higher tumor cell nucleic solidity (OR=3.048; 95%CI 1.513-6.138, P=0.002), but has lower nucleic solidity of the stroma cell (OR=0.253; 95%CI 0.097-0.665, P=0.005), lymphocyte (OR=0.081; 95%CI 0.017-0.392, P=0.002). Gal-9 is distinctively related to immune infiltration in LCNEC. The outcome of LNCEC can be predicted by integrated pathological analysis and Gal-9 based immune survival stratification.