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Inflamed immune phenotype predicts favorable clinical outcomes of immune checkpoint inhibitor therapy across multiple cancer types

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Shen, Jeanne; Choi, Yoon-La; Lee, Taebum; Kim, Hyojin; Chae, Young Kwang; Dulken, Ben W.; Bogdan, Stephanie; Huang, Maggie; Fisher, George A.; Park, Sehhoon; Lee, Se-Hoon; Hwang, Jun-Eul; Chung, Jin-Haeng; Kim, Leeseul; Song, Heon; Pereira, Sergio; Shin, Seunghwan; Lim, Yoojoo; Ahn, Chang Ho; Kim, Seulki; Oum, Chiyoon; Kim, Sukjun; Park, Gahee; Song, Sanghoon; Jung, Wonkyung; Kim, Seokhwi; Bang, Yung-Jue; Mok, Tony S. K.; Ali, Siraj M.; Ock, Chan-Young

Issue Date
BioMed Central
Journal for ImmunoTherapy of Cancer, Vol.12 No.2, p. 008339
Background The inflamed immune phenotype (IIP), defined by enrichment of tumor-infiltrating lymphocytes (TILs) within intratumoral areas, is a promising tumor-agnostic biomarker of response to immune checkpoint inhibitor (ICI) therapy. However, it is challenging to define the IIP in an objective and reproducible manner during manual histopathologic examination. Here, we investigate artificial intelligence (AI)-based immune phenotypes capable of predicting ICI clinical outcomes in multiple solid tumor types. Methods Lunit SCOPE IO is a deep learning model which determines the immune phenotype of the tumor microenvironment based on TIL analysis. We evaluated the correlation between the IIP and ICI treatment outcomes in terms of objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) in a cohort of 1,806 ICI-treated patients representing over 27 solid tumor types retrospectively collected from multiple institutions. Results We observed an overall IIP prevalence of 35.2% and significantly more favorable ORRs (26.3% vs 15.8%), PFS (median 5.3 vs 3.1 months, HR 0.68, 95% CI 0.61 to 0.76), and OS (median 25.3 vs 13.6 months, HR 0.66, 95% CI 0.57 to 0.75) after ICI therapy in IIP compared with non-IIP patients, respectively (p<0.001 for all comparisons). On subgroup analysis, the IIP was generally prognostic of favorable PFS across major patient subgroups, with the exception of the microsatellite unstable/mismatch repair deficient subgroup. Conclusion The AI-based IIP may represent a practical, affordable, clinically actionable, and tumor-agnostic biomarker prognostic of ICI therapy response across diverse tumor types.
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  • College of Medicine
  • Department of Medicine
Research Area Clinical Medicine


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