2621 Background: 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. Methods: 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). Results: 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 or TMB-high groups. Conclusions: 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.

2607 Background: Tumor infiltrating lymphocytes (TIL) are a potential tumor-agnostic biomarker for immune checkpoint inhibitor (ICI) therapy. We previously reported the clinical application of an artificial intelligence-powered spatial TIL analyzer, Lunit SCOPE IO, for predicting ICI treatment outcomes in advanced non-small cell lung cancer (NSCLC). Here, we expand the clinical application of Lunit SCOPE IO as a tumor-agnostic ICI biomarker across multiple cancer types. Methods: Lunit SCOPE IO was trained and validated with a 2.8 x 109 micrometer2 area and 5.9 x 106 TILs from 3,166 H&E Whole-Slide Images (WSI) of multiple cancer types, annotated by 52 board-certified pathologists. The Inflamed Score (IS) was defined as the proportion of all tumor-containing 1 mm2-size tiles within a WSI classified as being of the inflamed immune phenotype (high TIL density within cancer epithelium). We first evaluated the correlation between the IS and TMB, MSI-H, and immune cytolytic activity ( GZMA and PRF1) across 22 cancer types from The Cancer Genome Atlas (TCGA, n = 7,467). Subsequently, the correlation between the IS and overall survival after ICI treatment was evaluated in a real-world dataset of patients with 9 different tumor types (n = 1,013), retrospectively collected from Stanford University Medical Center, Chonnam National University Hospital, Samsung Medical Center, and Seoul National University Bundang Hospital. Results: Lunit SCOPE IO accurately detected CE, CS, and TILs with an area under the receiver-operating-characteristic curve of 0.970, 0.949, and 0.925, respectively. In the TCGA pan-cancer cohort, Lunit SCOPE IO’s IS correlated significantly with immune cytolytic activity (Spearman rho = 0.504, p < 0.001), TMB-high (≥ 10 mutations/Mb, fold change 1.39, p < 0.001) and MSI-H (fold change 1.45, p < 0.001). The IS-positive proportions of microsatellite-stable (MSS) and TMB-low cases were 42.5% and 17.1%, using the thresholds of IS ≥ 20% and ≥ 50% as presumptive clinical cutoffs. In the real-world ICI clinical dataset (n = 1,013), an IS ≥ 20% correlated significantly with favorable overall survival after ICI treatment (cancer type-adjusted hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.59-0.83, p < 0.0001). Furthermore, this association remained significant after the exclusion of NSCLC patients (n = 519) (adjusted HR 0.68, 95% CI 0.53-0.86, p = 0.0016) indicating that the effect was not driven solely by one major tumor type. Conclusions: The Inflamed Score (IS), as evaluated by Lunit SCOPE IO, correlates with favorable overall survival after ICI treatment across multiple tumor types. AI-powered spatial TIL analysis of the tumor microenvironment may be able to detect a significant proportion of ICI responders, and offers promise as a new companion diagnostic, particularly in patients with MSS/TMB-low tumors.

Connecting Young Minds (CYM) is an annual bilingual student-led research conference held at the University of Ottawa. Our mission is to encourage undergraduate students to network with professors, present their research, and gain experience drafting scientific literature. The conference engages the interests of students in the sciences through presentations held by keynote speakers, interactive breakout rooms with graduate level students, and a research-based competition. Each year, CYM hosts a 5-minute research presentation competition in which ten candidates are selected by a panel of judges based on the submission of an abstract pertaining to their research. The competition provides an opportunity for undergraduate students to highlight their research findings to an audience and series of judges in a concise and engaging manner. Abstracts in this booklet were submitted by participants on a volunteer basis.