Figure 7.
T-cell phenotypic features of spontaneously regressing tumors, reactivation of BCR signaling associated with relapse following spontaneous CLL regression, and biological processes underpinning spontaneous CLL regression. FACS analysis of the gated T-cell population of CLL PBMCs. (A) PD-1, LAG3, CD160, CD244, CTLA4, and Tim3 expression on CD4+ and CD8+ T cells in spontaneous regression cases (REG; n = 16) from the regression time point (T1) was compared against indolent cases (INDOL; n = 31) and age-matched healthy controls (CTRL; n = 6). (B) PD-1 expression in T cells was compared between the diagnostic (T0) and regression (T1) time points in individuals with spontaneous CLL regression. (C) Ki-67 expression in T cells of spontaneous regression cases (CTRL; n = 16) from the regression time point (T1) was compared against indolent cases (INDOL; n = 31) and age-matched healthy controls (CTRL; n = 6) and also between the diagnostic (T0) and regression (T1) time points in individuals with spontaneous CLL regression. (D) PBMCs from spontaneously regressed cases at maximal regression (n = 7) were incubated at 37°C for 48 hours in the presence and absence of CD40L-expressing fibroblasts and IL-4 (25 ng/mL), after which the CLL population was analyzed for Erk, Akt, and Syk phosphorylation in response to combined IgM/IgD BCR stimulation. Expression of (E) Ki-67 and (F) phosphoprotein response to combined BCR stimulation of PBMCs with anti-human IgM and IgD F(ab′)2 antibodies were compared between the regression (T1) and relapse (T2) time points of CLL20. (G) Schematic diagram illustrating the key biological processes underpinning spontaneous CLL regression (REG) and key differences as compared with nonregressing indolent (INDOL) and progressive (PROG) CLL. Statistical significance was determined using 1-way ANOVA with Bonferroni post hoc analysis between CLL cohorts and the paired Student t test between time points or stimulus. Statistical significance is indicated by *P < .05, **P < .01, ***P < .001, and ****P < .0001. ns, comparisons that are not statistically significant.

T-cell phenotypic features of spontaneously regressing tumors, reactivation of BCR signaling associated with relapse following spontaneous CLL regression, and biological processes underpinning spontaneous CLL regression. FACS analysis of the gated T-cell population of CLL PBMCs. (A) PD-1, LAG3, CD160, CD244, CTLA4, and Tim3 expression on CD4+ and CD8+ T cells in spontaneous regression cases (REG; n = 16) from the regression time point (T1) was compared against indolent cases (INDOL; n = 31) and age-matched healthy controls (CTRL; n = 6). (B) PD-1 expression in T cells was compared between the diagnostic (T0) and regression (T1) time points in individuals with spontaneous CLL regression. (C) Ki-67 expression in T cells of spontaneous regression cases (CTRL; n = 16) from the regression time point (T1) was compared against indolent cases (INDOL; n = 31) and age-matched healthy controls (CTRL; n = 6) and also between the diagnostic (T0) and regression (T1) time points in individuals with spontaneous CLL regression. (D) PBMCs from spontaneously regressed cases at maximal regression (n = 7) were incubated at 37°C for 48 hours in the presence and absence of CD40L-expressing fibroblasts and IL-4 (25 ng/mL), after which the CLL population was analyzed for Erk, Akt, and Syk phosphorylation in response to combined IgM/IgD BCR stimulation. Expression of (E) Ki-67 and (F) phosphoprotein response to combined BCR stimulation of PBMCs with anti-human IgM and IgD F(ab′)2 antibodies were compared between the regression (T1) and relapse (T2) time points of CLL20. (G) Schematic diagram illustrating the key biological processes underpinning spontaneous CLL regression (REG) and key differences as compared with nonregressing indolent (INDOL) and progressive (PROG) CLL. Statistical significance was determined using 1-way ANOVA with Bonferroni post hoc analysis between CLL cohorts and the paired Student t test between time points or stimulus. Statistical significance is indicated by *P < .05, **P < .01, ***P < .001, and ****P < .0001. ns, comparisons that are not statistically significant.

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