543 Integrated single-cell and spatial analysis of immune cell interactions in response to immune checkpoint blockade

• DOI: 10.1136/jitc-2024-sitc2024.0543
• Publication Date: 2024-11-05T14:58:58Z
• Authors: Athena Golfinos-O...; Taja Lozar; Parth Khatri; Rong Hu; Paul Lambert; Megan Fitzpatrick; Huy Q Dinh
• Keywords: Immune checkpoint

<h3>Background</h3> Like many cancer types, only ~20% of head and neck (HNC) patients respond favorably to immune checkpoint blockade (ICB) therapy. Previous single-cell RNA-Seq (scRNA-Seq) studies identified features, including macrophage subset ratios T-cell subtypes,^1–3 in HNC ICB outcomes. However, the spatial features HNC-infiltrated cells response treatment need be better characterized. Here we perform a systematic evaluation cell interactions between types within tumor microenvironment identify new therapeutic targets. <h3>Methods</h3> Here, generated omics data using complementary techniques from both 10X Visium spot-based transcriptomics (n=5 non-responders n=6 responders) Nanostring CosMx with 1000-gene (including 435 ligands receptors, allowing infer cell-cell interactions) 64-protein markers (70 microarray cores, n=13 n=11 performed comprehensive spatially defined tumors ICB-treated patients. Then, used integrated bioinformatics analyses cellular neighborhoods co-localizing proteomics data. In addition, publicly available scRNA-Seq^1–3 in-house constrained co-expressed Ligand-Receptor (LR) responder <h3>Results</h3> scRNA-Seq analysis ICB-responsive specific LR interaction candidates, known novel myeloid-T responders. Further CD45+ spots suggested enrichment chemokine signaling (CXCL13-CXCR3, CXCL9/10-CXCR3, CXCL16-CXCR6) responders pro-tumoral non-responders, SPP1-CD44, THBS1-CD47, THSB1-CD36). Our also dendritic subsets CXCR3+ T enriched as major sources CXCL9, an emerging marker for predicting over clinical PDL1 recent trial Cell-type co-presence neighborhood identification (CosMX) niches higher frequencies responders, tumor-CD8+ infiltration immune-stromal co-localization. Additionally, inference single showed elevated incoming CD8 highlighting interactions. <h3>Conclusions</h3> This work provides atlas that correlate HNC. We showcase how integrating multiple technologies approaches can provide insights into potential immune-based biomarkers response. Future will validate these findings elucidate underlying mechanisms lead improved responses. <h3>References</h3> Cillo AR, Kürten CHL, Tabib T, Qi Z, Onkar S, Wang Liu A, Duvvuri U, Kim Soose RJ, Oesterreich Chen W, Lafyatis R, Bruno TC, Ferris RL, Vignali DAA. Immune Landscape Viral- Carcinogen-Driven Head Neck Cancer. <i>Immunity</i> 2020 Jul 14;<b>53</b>(1):155–166.e5. doi: 10.1016/j.immuni.2020.06.002. Epub Jun 23. PMID: 32579887; PMCID: PMC7201194. Luoma AM, Suo Y, Gunasti L, Porter CBM, Nabilsi N, Tadros J, Ferretti AP, Liao Gurer C, YH, Criscitiello Ricker CA, Dionne D, Rozenblatt-Rosen O, Uppaluri Haddad RI, Ashenberg Regev Van Allen EM, MacBeath G, Schoenfeld JD, Wucherpfennig KW. Tissue-resident memory circulating are early pre-surgical immunotherapy.<i> Cell</i> 2022 Aug 4;<b>185</b>(16):2918–2935.e29. 10.1016/j.cell.2022.06.018. 7. 35803260; PMC9508682. Bill Wirapati P, Messemaker M, Roh Zitti B, Duval F, Kiss Park JC, Saal TM, Hoelzl Tarussio Benedetti Tissot Kandalaft Varrone Ciriello McKee TA, Monnier Mermod Blaum Gushterova I, Gonye ALK, Hacohen Getz Mempel TR, Klein Weissleder Faquin WC, Sadow PM, Lin Pai SI, Sade-Feldman Pittet MJ. CXCL9:SPP1 polarity identifies network programs control human cancers. <i>Science</i> 2023 4;<b>381</b>(6657):515–524. 10.1126/science.ade2292. 3. 37535729; PMC10755760.