Intratumoral changes in critical lymphocyte populations and numbers after NKTR-214 treatment. Intratumoral changes in critical lymphocyte populations and.

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Intratumoral changes in critical lymphocyte populations and numbers after NKTR-214 treatment. Intratumoral changes in critical lymphocyte populations and numbers after NKTR-214 treatment. Tumor biopsies were obtained at baseline (blue) and after NKTR-214 treatment (orange). Immune infiltrates, including CD45+ live cells, NK cells, and CD8+ T cells, were analyzed by flow cytometry on freshly disaggregated tumor tissue. Patients #13 and #14 received a NKTR-214 dose of 0.006 mg/kg q2w. A, Percentage of live CD45+ cells within total cells. B, Percentage of NK cells (top plot) and CD8+ T cells (bottom plot) within CD45+ live cells. C, A portion of the tumor biopsy from the chest wall of a patient with RCC (#13) dosed q2w was further analyzed for CD8 staining by IHC (left), 10 patients had pretreatment and on-treatment IHC data (right), and each circle represents one individual tumor sample with red circles indicating increased and black circles indicating similar or reduced number of CD8+ T cells on-treatment compared with pretreatment. D, TCR sequencing examining the percentage of T-cell infiltration (the fraction productive of cells mass estimate values obtained through the immuSeq Analyzer software; top plot) and clonality (bottom plot) in tumor biopsy samples, n = 12. E, Percentage of CD4+CD25hiFOXP3+ Tregs within total CD4+ T cells in the blood before and 8 days after treatment with NKTR-214. A representative result is shown on the left. Paired t test, **, P < 0.01. F, Percentage of CD4+CD25hiFOXP3+ Tregs within CD3+ T cells in tumor biopsies samples was analyzed by flow cytometry, n = 14. G, Quantification of the number of FOXP3+ cells by IHC, n = 10, and each circle represents one individual tumor sample with red circles indicating increased and black circles indicating unchanged or reduced FOXP3+ cells on-treatment compared with pretreatment. H, PD-1 expression within CD4+ (top plot) and CD8+ T cells (bottom plot) in tumor biopsy samples was analyzed by flow cytometry (n = 14). Salah-Eddine Bentebibel et al. Cancer Discov 2019;9:711-721 ©2019 by American Association for Cancer Research