163 A multi-modal, pan-cancer atlas of tumor-immune states across primary and metastatic disease using a large, real-world database

• DOI: 10.1136/jitc-2023-sitc2023.0163
• Publication Date: 2023-10-31T13:42:15Z
• Authors: Prerna Jain; Michelle M Stein; Paul Fields; Bolesław Osinski; Luca Lonini; Ariane Lozac’hmeur; Rohan Joshi; Halla Nimeiri; Martin Stumpe; Kate Sasser; Catherine Igartua; Justin Guinney; Mary L Disis
• Keywords: Cancer Immunotherapy

<h3>Background</h3> Immuno-oncology (IO) therapies have demonstrated effective and durable benefits in multiple cancer indications but responses are variable. Discovery validation of better biomarkers treatment response, ability to modulate immunological states, selection optimal drug combinations, identification new IO targets top priorities maximize the clinical impacts immunotherapy. While immune tumor microenvironment been well-characterized primary tumors,¹ large-scale assessments metastatic disease lacking. Here, we conducted a multi-modal, pan-cancer analysis comparing states across using real-world database. <h3>Methods</h3> Analysis was Tempus platform, encompassing molecular data immunophenotyping algorithms layered upon large, patient To date, platform comprises over 200k de-identified records with pre-computed immunophenotypes (<i>e.g.</i> cell fraction, HLA typing quantification, TCR/BCR diversity, TIL estimation from H&amp;E) dozens types, 20k cases treated therapy. Somatic DNA alterations whole-exome transcriptomes were profiled xT xR NGS assays, respectively, optimized probes for profiling. <h3>Results</h3> A landscape, multi-modal comparison performed on 70k records, comprising diverse spectrum tissue sites, prognostic stages. Analyses bulk RNA showed liver mets significantly lower infiltration, higher macrophage TCR diversity compared lung met tumors (P&lt;0.001) (figure 1). quantification 104 NSCLC digitized H&amp;E slides revealed significant correlation between intratumoral density cytotoxic T-cell score (ρ=0.57, P&lt;0.001) 2A), confirmed versus (P&lt;0.01) 2B). In stratified Cox regression types first-line checkpoint blockade (N=1623), IO-response signatures^2–4 highly predictive OS (P&lt;0.001)(figure 3A), superior TMB, exhibited differential enrichment sites 3B). <h3>Conclusions</h3> largest differences observed by indication, important implications IO-treatment strategies. These provide valuable timely insights research, where simultaneous assessment molecular, immune, traits is required. <h3>References</h3> Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang T-H, <i>et al.</i> The Immune Landscape Cancer. <i>Immunity</i>. 2019;<b>51</b>:411–2. Ayers M, Lunceford J, Nebozhyn Murphy E, Loboda A, Kaufman DR, IFN-γ-related mRNA profile predicts response PD-1 blockade. <i>J Clin Invest. American Society Clinical Investigation</i>; 2017;<b>127</b>:2930–40. Lau Khare S, Stein MM, Jain P, Gao Y, BenTaieb Integration extrinsic intrinsic features associates immunotherapy non-small cancer. <i>Nat Commun</i>. 2022;<b>13</b>:4053. Huang AC, Orlowski RJ, Xu X, Mick R, George SM, Yan PK, single dose neoadjuvant outcomes resectable melanoma. Med</i>. 2019;<b>25</b>:454–61. <h3>Ethics Approval</h3> under exemption Pro00042950 granted Advarra, Inc. Institutional Review Board (IRB). Per this exemption, written informed consent not All methods carried out accordance relevant guidelines regulations.