Higher TLT-1 expression is associated with reduced survival of NSCLC patients and tumor CD8 T cell exhaustion. (A) The survival curves (KM-plot) for the present study cohort showing significant difference (logrank Mantel–Cox P value = 0.036) between OS of patients with very high (≥200) platelet surface TLT-1 expression as measured by FC (normalized as % change over control) as compared to those with relatively lower levels (<200). The 200 cut-off was chosen because the median percent increase for these patients was very close (190) to this value. The plot shows follow up of a maximum of 3 yr for this cohort (logrank Mantel–Cox test). (B) The KM-plots for median 10-yr OS survival of NSCLC patients plotted with TLT-1 expression are shown as extracted from the KM plotter database, showing significantly (P < 0.0001) reduced OS. The details of patient cohorts used for generating the presented survival curve (B) are given in Fig. S5 B. The logrank test hazard ratio (HR) values along with 95% confidence interval range shown for each plot. (C) The NSCLC patient lung sections (representative for n = 6, with 6–10 frames per section) with positive TLT-1 staining (red) showing increased TLT-1 and reduced CD8 T cells (violet) in tumor-rich areas as compared to the tumor-poor areas from lung biopsy samples of same patient. The PanCK marker (cyan) was used for identifying tumor cells; CD3 (green) was used as a T cell marker. The original magnification was 200×, and the scale bar equals 100 µm. (D) TIMER, a webtool, was used to assess the relationship between TLT-1 and CD8 T cell infiltration in lung adenocarcinoma tumors using previous high-throughput gene datasets. The TLT-1 expression shows significant correlations with T cell exhaustion markers—CTLA-4, PDCD-1 (PD-1), and TIM-3 in tumor microenvironment. The correlation coefficient and P values are shown. The experimental data represent a minimum of two independent experiments.
Figure 5.

Higher TLT-1 expression is associated with reduced survival of NSCLC patients and tumor CD8 T cell exhaustion. (A) The survival curves (KM-plot) for the present study cohort showing significant difference (logrank Mantel–Cox P value = 0.036) between OS of patients with very high (≥200) platelet surface TLT-1 expression as measured by FC (normalized as % change over control) as compared to those with relatively lower levels (<200). The 200 cut-off was chosen because the median percent increase for these patients was very close (190) to this value. The plot shows follow up of a maximum of 3 yr for this cohort (logrank Mantel–Cox test). (B) The KM-plots for median 10-yr OS survival of NSCLC patients plotted with TLT-1 expression are shown as extracted from the KM plotter database, showing significantly (P < 0.0001) reduced OS. The details of patient cohorts used for generating the presented survival curve (B) are given in Fig. S5 B. The logrank test hazard ratio (HR) values along with 95% confidence interval range shown for each plot. (C) The NSCLC patient lung sections (representative for n = 6, with 6–10 frames per section) with positive TLT-1 staining (red) showing increased TLT-1 and reduced CD8 T cells (violet) in tumor-rich areas as compared to the tumor-poor areas from lung biopsy samples of same patient. The PanCK marker (cyan) was used for identifying tumor cells; CD3 (green) was used as a T cell marker. The original magnification was 200×, and the scale bar equals 100 µm. (D) TIMER, a webtool, was used to assess the relationship between TLT-1 and CD8 T cell infiltration in lung adenocarcinoma tumors using previous high-throughput gene datasets. The TLT-1 expression shows significant correlations with T cell exhaustion markers—CTLA-4, PDCD-1 (PD-1), and TIM-3 in tumor microenvironment. The correlation coefficient and P values are shown. The experimental data represent a minimum of two independent experiments.

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