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. 2023 Nov 10;11(11):e007697. doi: 10.1136/jitc-2023-007697

Figure 3.

Figure 3

Therapy-induced changes in the circulation. (A–D) White blood cell counts were performed on blood samples obtained at the indicated time points before and during treatment. Shifts from baseline in absolute (A) lymphocyte, (B) monocyte, and (C) neutrophil cell counts (×109/L) are shown. (D) Changes in the ratio of myeloid (neutrophils (PMN) and monocytes (M)) cells to lymphocytes are depicted. (E–I) Plasma samples were collected at the indicated time points before and during treatment to assess changes in circulating cytokine levels. The levels of (E) IL-7, (F) IL-15, (G) IL-21, and (H) IL-6 cytokines were analyzed by ELISA. (I) The correlation between circulating myeloid cell frequencies and IL-6 cytokine levels is shown by linear regression. P6-pre, indicates the high IL-6 level corresponding to high myeloid cell frequency observed in P6 prior to treatment. (J–N) Treatment effect on circulating lymphocyte and antigen presenting cell function was assessed in peripheral blood mononuclear cells isolated from venous blood samples collected at the indicated time-points before and during treatment. The proliferative response of lymphocytes to (J) influenza M1 (influenza) antigen, (K) memory response mix (MRM) and (L) CD3/CD28 activation beads, was measured by 3H-thymidine incorporation. The changes are depicted as shift from baseline of the proliferation index. (M) The APC function was evaluated using a mixed lymphocyte reaction (MLR). (N) The correlation between APC function (MLR change from baseline) and reduction in circulating monocyte numbers (shift from baseline) is shown by linear regression. The gray areas indicate the period when the three consecutive TIL infusions were administered. Results for the patient with a durable CR (P6) are depicted in green. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 indicate significant changes from baseline by Kruskal-Wallis with Dunn’s correction for multiple comparisons. CR, complete response.