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Research Article

Deep immune profiling of ovarian tumors identifies minimal MHC-I expression after neoadjuvant chemotherapy as negatively associated with T-cell-dependent outcome

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Article: 1760705 | Received 25 Jul 2019, Accepted 30 Jan 2020, Published online: 13 May 2020

Figures & data

Figure 1. Immune contexture is defined by the tissue of origin, independent of chemotherapy.

Figure 1. Immune contexture is defined by the tissue of origin, independent of chemotherapy.

Figure 2. Immune cell distribution is comparable between pre- and post-chemotherapy tumors. (a) Epithelial infiltration of CD3+, CD8+, CD27+, PD1+, FoxP3+, and CD20+ cells in pre- and post-chemotherapy tumors. Density is defined as cells/mm2. (b) Stromal infiltration of CD3+, CD8+, CD27+, PD1+, FoxP3+, and CD20+ cells in pre- and post-chemotherapy tumors. Density is defined as cells/mm2. (c) Epithelial and stromal infiltration of CD16+ cells in pre- and post-chemotherapy tumors. Epithelial infiltration was determined by density in cells/mm2, stromal infiltration was determined by the percentage of positive area. (d) Epithelial infiltration of CD11 c+, LAMP3+, CD68+, and CD163+ cells in pre- and post-chemotherapy tumors. Density is defined as cells/mm2. (e) Stromal infiltration of CD11 c+, LAMP3+, CD68+, and CD163+ cells in pre- and post-chemotherapy tumors. Stromal infiltration is determined by the percentage of positive area. (f) Epithelial and stromal infiltration of PD-L1+ cells in pre- and post-chemotherapy tumors. Infiltration was determined by the percentage of positive area. (a–f) Representative samples are depicted in supplementary figure S5. Differences in the number of tumor-infiltrating immune cells on FFPE slides were determined by two-tailed Mann Whitney test. N-numbers are described in supplementary table S3 C. G, Median immune cell density of all epithelial and stromal immune cells depicted in a–f. Comparability between pre- and post-chemotherapy tumors was determined by a Pearson correlation test. R2 = 0.92, <0.0001.

Figure 2. Immune cell distribution is comparable between pre- and post-chemotherapy tumors. (a) Epithelial infiltration of CD3+, CD8+, CD27+, PD1+, FoxP3+, and CD20+ cells in pre- and post-chemotherapy tumors. Density is defined as cells/mm2. (b) Stromal infiltration of CD3+, CD8+, CD27+, PD1+, FoxP3+, and CD20+ cells in pre- and post-chemotherapy tumors. Density is defined as cells/mm2. (c) Epithelial and stromal infiltration of CD16+ cells in pre- and post-chemotherapy tumors. Epithelial infiltration was determined by density in cells/mm2, stromal infiltration was determined by the percentage of positive area. (d) Epithelial infiltration of CD11 c+, LAMP3+, CD68+, and CD163+ cells in pre- and post-chemotherapy tumors. Density is defined as cells/mm2. (e) Stromal infiltration of CD11 c+, LAMP3+, CD68+, and CD163+ cells in pre- and post-chemotherapy tumors. Stromal infiltration is determined by the percentage of positive area. (f) Epithelial and stromal infiltration of PD-L1+ cells in pre- and post-chemotherapy tumors. Infiltration was determined by the percentage of positive area. (a–f) Representative samples are depicted in supplementary figure S5. Differences in the number of tumor-infiltrating immune cells on FFPE slides were determined by two-tailed Mann Whitney test. N-numbers are described in supplementary table S3 C. G, Median immune cell density of all epithelial and stromal immune cells depicted in a–f. Comparability between pre- and post-chemotherapy tumors was determined by a Pearson correlation test. R2 = 0.92, <0.0001.

Figure 3. T-cell differentiation is heterogeneous across tissue types.

Figure 3. T-cell differentiation is heterogeneous across tissue types.

Figure 4. ICOS, GITR, and CTLA-4 co-expression.

Figure 4. ICOS, GITR, and CTLA-4 co-expression.

Figure 5. PD-1+ cells only have a survival benefit in pre-chemotherapy tumors who were completely removed after primary surgical debulking.

Figure 5. PD-1+ cells only have a survival benefit in pre-chemotherapy tumors who were completely removed after primary surgical debulking.

Figure 6. Treatment of HGSOC patients with neoadjuvant chemotherapy is associated with minimal expression of MHC-I.

Figure 6. Treatment of HGSOC patients with neoadjuvant chemotherapy is associated with minimal expression of MHC-I.
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