Deep learning-based H&E analyzer can classify the tumor microenvironment as three immune phenotypes: the immune-inflamed, excluded and desert. Our previous study demonstrated a distinct transcriptomic and immunologic landscape amongst the phenotypes in non-small cell lung cancer (NSCLC). However, it has not been fully investigated in other cancers. Here, we explore the immune profiles and clinical outcomes between the three immune phenotypes in uterine corpus endometrial carcinoma (UCEC).
Tissue H&E slide images, sequencing data, and clinical data were utilized from The Cancer Genome Atlas (TCGA). Lunit-SCOPE IO was trained with multi-cancer 3,166 H&E whole slide images annotated by pathologists. Based on the proportion of tumor infiltrating lymphocytes (TIL) highly conserved either in cancer epithelium (CE) or cancer stroma (CS), Lunit-SCOPE IO classifies tumors as immune-inflamed and excluded, respectively. Also, it classifies tumors with low TIL density in CE and CS as immune-desert.
Among 486 patients with UCEC, the frequency of immune-inflamed, excluded and desert was 174 (35.8%), 160 (32.9%), and 156 (32%), respectively. In the three subgroup comparison, immune-inflamed was associated with the best survival outcome and -excluded was associated with the worst survival outcome (Inflamed vs excluded, HR 0.30 95% CI 0.17-0.55, p<.001; desert vs excluded, HR 0.50 95% CI 0.30-0.84, p=0.009). Likewise, inflamed subtype showed better overall survival (HR 0.43, 95% CI 0.25-0.75, p=0.003) compared to others. In microsatellite instability high (MSI-H) tumors, we observed a similar tendency of improved overall survival in the tumors of inflamed subtype, both compared to the excluded subtype and to a combination of other subtypes. (Inflamed vs excluded, HR 0.18 95% CI 0.05-0.73, p=0.017; inflamed vs others, HR 0.21 95% CI 0.06-0.72, p=0.014). Immune-inflamed had significantly higher cytolytic activity (Inflamed 7.25 vs others 6.34, p<.001) and was associated with higher PD-L1 expression (Inflamed 19.03 vs others 10.7, p=0.003) and CTLA4 expression (Inflamed 60.62 vs others 31.5, p<.001). Immune-inflamed had a higher proportion of CD8 positive T cell (Inflamed 16.7% vs 12.8%, p<.001) and M1 macrophage (Inflamed 3.9% vs others 2.8%, p<.001) and a lower proportion of M2 macrophage (Inflamed 15% vs others 17.9%, p<.001).
The three tissue phenomic subtypes showed distinct immune profiles and clinical outcomes, with immune-inflamed having the best overall survival outcome. In particular, non-inflamed group was associated with worse overall survival even in MSI-H tumors deemed to have more favorable prognosis compared to MSS tumors. Given the definite differences in the survival outcome, tissue H&E based tumor microenvironment classification may serve as a potential prognostic biomarker in UCEC.
Horyun Choi, Leeseul Kim, Jinah Kim, Yeun Ho Lee, Hyung-Gyo Cho, Na Hyun Kim, Gahyun Gim, Sanghoon Song, Gahee Park, Soo Ick Cho, Sergio Pereira, Donggeun Yoo, Kyunghyun Paeng, Chan-Young Ock, Young Kwang Chae.
University of Hawaii Internal Medicine Residency Program, Honolulu, HI, AMITA Health Saint Francis Hospital Evanston, Evanston, IL, UPMC Harrisburg, Harrisburg, PA, Northwestern University Feinberg School of Medicine, Chicago, IL, Lunit, Seoul, Korea, Republic of, AMITA St Joseph Hospital Chicago, Chicago, IL, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY