Back to List

The Inflamed Immune Phenotype (IIP): a clinically actionable artificial intelligence (AI)-based biomarker predictive of immune checkpoint inhibitor (ICI) outcomes across >16 primary tumor types

Jeanne Shen et al. — ASCO(2022)



The IIP, defined by enriched intratumoral tumor-infiltrating lymphocytes (TIL), is a potential tumor-agnostic biomarker of responsiveness to ICI therapy. Here, we validate the IIP, as assessed by Lunit SCOPE IO, an AI-powered spatial TIL analyzer that runs on routine H&E-stained whole-slide images (WSI), for clinical outcome prediction in a large, multi-center international cohort of ICI-treated patients, demonstrating its utility as a practical biomarker to guide ICI treatment planning. 


Lunit SCOPE IO was developed using 17,849 H&E WSI of multiple cancer types, annotated by 104 board-certified pathologists (13.5 x 109 µm2 area and 6.2 x 106 TIL). IIP+ tumors were defined as those with ≥ 20% of all 1 mm2 tumor tiles in a WSI classified as having a high intratumoral TIL density. We evaluated the correlation between IIP and ICI treatment outcomes (overall response rate (ORR) and progression-free survival (PFS), assessed by RECIST v1.1) in a real-world dataset of 1,806 patients (>16 primary tumor types) retrospectively collected from Stanford University Medical Center, Samsung Medical Center, Chonnam National University Hospital, Seoul National University Bundang Hospital, and Northwestern University. IIP status was sub-analyzed by PD-L1 22C3 tumor proportion score (TPS, n = 798), microsatellite status, and tumor mutational burden (TMB, n = 130).


The IIP+ phenotype (35.2%, 636 of 1,806) was highly enriched in nasopharyngeal carcinoma (68.0%), melanoma (56.3%), renal cell carcinoma (52.9%), and non-small cell lung cancer (NSCLC, 33.7%). The IIP+ proportion by PD-L1 TPS (< 1% / ≥ 1%) was 21.6% and 40.7%, respectively. While 33.3% of microsatellite unstable (MSI-H) or TMB-high (≥ 10/Mb) tumors were IIP+, a substantial proportion (26.1%) of microsatellite stable (MSS), TMB-low tumors were IIP+. The ORR in IIP+ patients was significantly higher (26.0% vs. 15.8% in IIP-, p < 0.001). Median PFS for IIP+ was 5.3 months (95% CI 4.6-6.9 m), significantly longer than that for IIP- (3.1 m, 95% CI 2.8-3.6 m), with a hazard ratio (HR) of 0.68 (95% CI 0.61-0.76, p < 0.001). The association held after excluding NSCLC patients (n = 909) (HR 0.69, 95% CI 0.59-0.81, p < 0.001). On subgroup analysis, IIP+ correlated significantly with prolonged PFS, regardless of ICI regimen (mono / combo therapy) or PD-L1 TPS (< 1% / ≥ 1%). Of note, IIP+ was predictive of favorable PFS only in the MSS/TMB-low group (n = 88, HR 0.56, 95% CI 0.33-0.96), but not in the MSI-H/TMB-high groups.


The IIP, as evaluated by Lunit SCOPE IO, may represent a practical, clinically-actionable biomarker predictive of favorable ICI treatment outcomes across diverse cancer patient populations, including those with PD-L1 negative, MSS/TMB-low tumors, in whom predictive biomarkers are urgently needed.

Read the full paper

Jeanne Shen1,2, Yoon-La Choi3, Taebum Lee4, Hyojin Kim5, Young Kwang Chae6, Benjamin Dulken1, Stephanie Bogdan2, Maggie Huang7, George A. Fisher, Jr.8, Sehhoon Park9, Se-Hoon Lee9, Jun-Eul Hwang10, Jin-Haeng Chung5, Leeseul Kim11, Seunghwan Shin12, Yoojoo Lim12, Heon Song12, Sergio Pereira12, Chan-Young Ock12.

1Department of Pathology, Stanford University School of Medicine. 2Center for Artificial Intelligence in Medicine & Imaging, Stanford University. 3Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 4Department of Pathology, Chonnam National University Medical School, Republic of Korea. 5Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. 6Northewestern University. 7UC Davis Health

8Department of Medicine, Stanford University School of Medicine. 9Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 10Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School, Republic of Korea. 11AMITA health Saint Francis Hospital Evanston, Evanston IL, United States. 12Lunit Inc., Seoul, Republic of Korea.


Read more