Figure 3 from Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer
Authors: Enfield Katey S.S. , Colliver Emma , Lee Claudia , Magness Alastair , Moore David A. , Sivakumar Monica , Grigoriadis Kristiana , Pich Oriol , Karasaki Takahiro , Hobson Philip S. , Levi Dina , Veeriah Selvaraju , Puttick Clare , Nye Emma L. , Green Mary , Dijkstra Krijn K. , Shimato Masako , Akarca Ayse U. , Marafioti Teresa , Salgado Roberto , Hackshaw Allan , Jamal-Hanjani Mariam , van Maldegem Febe , McGranahan Nicholas , Glass Benjamin , Pulaski Hanna , Walk Eric , Reading James L. , Quezada Sergio A. , Hiley Crispin T. , Downward Julian , Sahai Erik , Swanton Charles , Angelova Mihaela 
Published: June 2024

<p>Spatial features associated with neoantigen burden and immune low TMEs. <b>A,</b> Correlation of densities of spatial cellular communities and the burden of expressed clonal, subclonal and total neoantigens predicted to bind intact HLA alleles, after accounting for HLA LOH, in LUAD (<i>n</i> = 31, 51 tumor cores) and LUSC (<i>n</i> = 17, 37 tumor cores). Bar plot shows the median neoantigen burden with whiskers extending to the 75th percentile. <b>B,</b> Comparison of the densities of spatial cellular communities in a given TME class compared with all other TME classes combined. LUAD: <i>n</i> = 21 <i>TS:TIL+M<i>Φ</i> high</i> cores, <i>n</i> = 20 <i>T:TIL+M<i>Φ</i> excluded</i> cores, <i>n</i> = 13 <i>TS:Immune low</i> cores, <i>n</i> = 11 <i>TS:Neutrophil high</i> cores. LUSC: <i>n</i> = 13 <i>TS:TIL+M<i>Φ</i> high</i> cores, <i>n</i> = 12 <i>T:TIL+M<i>Φ</i> excluded</i> cores, <i>n</i> = 8 <i>TS:Immune low</i> cores, <i>n</i> = 15 <i>TS:Neutrophil high</i> cores. Box sizes in <b>A</b> and <b>B</b> correspond to T values. <b>C,</b> Community and cell subtype maps from a LUAD tumor core with a high burden of expressed clonal neoantigens and high densities of <i>C2:T-cell enriched</i> and <i>C6:macrophage and T cells</i> communities. <b>D,</b> Community and cell subtype maps from a LUSC tumor core with a high burden of expressed clonal neoantigens and high densities of community <i>C9:B cells and plasma cells</i>. Single cells in <b>C</b> and <b>D</b> are colored by community according to the color legend below <b>D</b> or cell subtype as indicated. Scale bars, 200 μm. Middle, an enlargement of the area highlighted with a white box in the left plot with matched cell subtypes shown in the right plot. <b>E,</b> Schematic of αSMA<sup>+</sup> fibroblast barrier score calculation. The barrier score measures the degree of spatial interpositioning of tumor cell–adjacent αSMA<sup>+</sup> fibroblasts between CD8 T cells and their nearest tumor cell(s) in a tissue core. In the lower half of the schematic, three nearest tumor cells are defined for the green CD8 T cell, all six hops away. Tumor cell–adjacent αSMA<sup>+</sup> fibroblasts are found on two of these three paths from CD8 T-cell to tumor cell, resulting in a barrier score of ⅔. <b>F,</b> Boxplot comparing the αSMA<sup>+</sup> fibroblast barrier scores in a given TME class compared with all other TME classes combined in LUAD (<i>n</i> = 36, 57 tumor cores) and LUSC (<i>n</i> = 22, 45 tumor cores). Boxplots show median and lower and upper quartile values, and whiskers extend up to 1.5 × IQR above and below the quartiles. <b>G,</b> Representative IMC images and cell type maps from LUAD and LUSC tumor cores classified as <i>TS:Immune low</i> with a high barrier score. Scale bars, 200 μm. <i>P</i> values in <b>A</b>, <b>B</b>, and <b>F</b> and T values in <b>A</b> and <b>B</b> were calculated in a linear mixed-effects model with patient as a random effect, using smoking status as a fixed effect in <b>A</b> with a <i>P</i> value < 0.05 considered significant. LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; panCK, pancytokeratin; TS, tumor/stroma; T, tumor; TIL, tumor-infiltrating lymphocytes; MΦ, macrophage; *, <i>P</i> < 0.05; **, <i>P</i> < 0.01.</p>