T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Demographics of HCC Patients
2.2. Outcomes
2.3. Distribution of Immune Cells in Different Regions of Interest (ROIs)
2.4. Prognostic Values of Immune Cells
2.5. Association between Subtypes of Immune Cells and Clinical and Pathology Variables
3. Discussion
3.1. Heterogeneity of the Tumor Invasive Margin
3.2. CD8+ Cells in TC and CD20+ Cells in the Inner Margin Confer the Best Prediction of TTR and DFS
3.3. CD8+ and CD20+ Cells in the Inner Margin Cooperate in Initiating Antitumor Immune Response
3.4. Greater T- and B-Cell Ratios between Inner and Outer Margin Associate with Longer TTR and DFS
3.5. Comparison to Relevant Literature
3.6. Limitations
4. Patients and Methods
4.1. Pathology and Immunohistology
4.2. Definitions of Regions of Interest
4.3. Stereological Analysis
4.4. Prognostic Factors and Outcomes
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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QA | TTR | DFS | |||||
---|---|---|---|---|---|---|---|
HR | 95% CI | p | HR | 95% CI | p | ||
Tumor Center | |||||||
CD3,n = 67 p = 0.030 *, 0.014 † | int vs. low | 0.61 | 0.26–1.40 | 0.243 | 0.62 | 0.31–1.23 | 0.170 |
high vs. low | 0.20 | 0.06–0.66 | 0.008 | 0.28 | 0.12–0.66 | 0.003 | |
CD8,n = 67 p = 0.010 *, 0.004 † | int vs. low | 0.34 | 0.14–0.81 | 0.014 | 0.53 | 0.27–1.07 | 0.075 |
high vs. low | 0.25 | 0.09–0.70 | 0.008 | 0.23 | 0.09–0.55 | 0.001 | |
CD20,n = 67 p = 0.031 *, 0.020 † | int vs. low | 0.63 | 0.27–1.48 | 0.289 | 0.67 | 0.32–1.37 | 0.270 |
high vs. low | 0.18 | 0.05–0.65 | 0.009 | 0.27 | 0.11–0.69 | 0.006 | |
Inner invasive margin | |||||||
CD3,n = 65 p = 0.014 *, 0.005 † | int vs. low | 0.77 | 0.33–1.79 | 0.545 | 0.77 | 0.39–1.55 | 0.472 |
high vs. low | 0.14 | 0.04–0.54 | 0.004 | 0.24 | 0.09–0.59 | 0.002 | |
CD8,n = 66 p = 0.029 *, 0.006 † | int vs. low | 0.52 | 0.23–1.19 | 0.120 | 0.77 | 0.40–1.51 | 0.455 |
high vs. low | 0.23 | 0.08–0.69 | 0.009 | 0.22 | 0.09–0.57 | 0.002 | |
CD20,n = 66 p = 0.002 *, <0.001 † | int vs. low | 0.38 | 0.16–0.90 | 0.026 | 0.36 | 0.18–0.74 | 0.005 |
high vs. low | 0.09 | 0.02–0.36 | 0.001 | 0.13 | 0.05–0.35 | <0.001 | |
Outer invasive margin | |||||||
CD3,n = 65 p = 0.354 *, 0.280 † | int vs. low | 0.66 | 0.26–1.65 | 0.371 | 0.58 | 0.27–1.23 | 0.153 |
high vs. low | 0.47 | 0.17–1.32 | 0.151 | 0.56 | 0.26–1.24 | 0.153 | |
CD8,n = 66 p = 0.325 *, 0.061 † | int vs. low | 0.55 | 0.22–1.37 | 0.197 | 0.48 | 0.23–0.98 | 0.044 |
high vs. low | 0.50 | 0.18–1.36 | 0.174 | 0.41 | 0.18–0.92 | 0.030 | |
CD20,n = 66 p = 0.680 *, 0.475 † | int vs. low | 0.99 | 0.40–2.44 | 0.986 | 0.99 | 0.49–2.00 | 0.974 |
high vs. low | 0.68 | 0.25–1.87 | 0.452 | 0.65 | 0.29–1.45 | 0.290 | |
Peritumor liver | |||||||
CD3, n = 64 | int vs. low | 0.53 | 0.20–1.38 | 0.193 | 0.74 | 0.34–1.63 | 0.452 |
p = 0.418 *, 0.676 † | high vs. low | 0.78 | 0.30–2.04 | 0.608 | 0.95 | 0.42–2.14 | 0.902 |
CD8, n = 65 | int vs. low | 0.82 | 0.33–2.04 | 0.663 | 1.09 | 0.52–2.26 | 0.828 |
p = 0.753 *, 0.952 † | high vs. low | 1.15 | 0.43–3.04 | 0.780 | 1.14 | 0.50–2.62 | 0.757 |
CD20, n = 65 | int vs. low | 0.24 | 0.09–0.64 | 0.004 | 0.43 | 0.20–0.92 | 0.030 |
p= 0.014 *, 0.053 † | high vs. low | 0.72 | 0.30–1.71 | 0.452 | 0.86 | 0.40–1.84 | 0.699 |
TTR | DFS | |||||
---|---|---|---|---|---|---|
HR | 95% CI | p | HR | 95% CI | p | |
CD3+ T cells | ||||||
Inn M/out M > 0.361 †, n = 65 | 0.36 | 0.16–0.85 | 0.019 | 0.45 | 0.24–0.86 | 0.016 |
TC/out M > 0.201, n = 65 | 0.41 | 0.18–0.92 | 0.031 | 0.56 | 0.31–1.02 | 0.057 |
TC/M > 0.330, n = 65 | 0.53 | 0.24–1.17 | 0.117 | 0.64 | 0.35- 1.16 | 0.138 |
TC/PT > 0.219, n = 64 | 0.43 | 0.19–1.00 | 0.050 | 0.61 | 0.33–1.13 | 0.116 |
CD8+ T cells | ||||||
Inn M/out M > 0.349, n = 66 | 0.53 | 0.24–1.17 | 0.119 | 0.45 | 0.24–0.85 | 0.013 |
TC/out M > 0.166, n = 66 | 0.59 | 0.27–1.29 | 0.187 | 0.63 | 0.34–1.15 | 0.131 |
TC/M > 0.218, n = 66 | 0.76 | 0.36–1.62 | 0.478 | 0.85 | 0.47–1.54 | 0.598 |
TC/PT > 0.161, n = 65 | 0.41 | 0.18–0.93 | 0.032 | 0.42 | 0.22–0.81 | 0.010 |
CD20+ B cells | ||||||
Inn M/out M > 0.113, n = 66 | 0.28 | 0.12–0.65 | 0.003 | 0.29 | 0.15–0.57 | <0.001 |
TC/out M > 0.051, n = 66 | 0.23 | 0.09–0.54 | 0.001 | 0.40 | 0.21–0.75 | 0.004 |
TC/M > 0.078, n = 66 | 0.24 | 0.10–0.57 | 0.001 | 0.41 | 0.22–0.76 | 0.005 |
TC/PT > 0.049, n = 65 | 0.27 | 0.12–0.65 | 0.003 | 0.49 | 0.27–0.90 | 0.022 |
TTR | ||||
---|---|---|---|---|
HR | 95% CI | p | ||
Density of nucleated profiles of TIL (QA) per ROI | ||||
CD3 TC † p = 0.082 * | int vs. low | 0.78 | 0.32–1.96 | 0.601 |
high vs. low | 0.26 | 0.07–0.89 | 0.032 | |
CD8 TC p = 0.010 * | int vs. low | 0.34 | 0.14–0.81 | 0.014 |
high vs. low | 0.25 | 0.09–0.70 | 0.008 | |
CD20 TC † p = 0.017 * | int vs. low | 0.91 | 0.35–2.35 | 0.842 |
high vs. low | 0.18 | 0.05–0.64 | 0.008 | |
CD3 inn M † p = 0.014 * | int vs. low | 1.02 | 0.41–2.53 | 0.961 |
high vs. low | 0.16 | 0.04–0.62 | 0.008 | |
CD8 inn M † p = 0.065 * | int vs. low | 0.60 | 0.25–1.39 | 0.230 |
high vs. low | 0.26 | 0.09–0.81 | 0.020 | |
CD20 inn M † p = 0.004 * | int vs. low | 0.50 | 0.20–1.27 | 0.147 |
high vs. low | 0.10 | 0.03–0.39 | 0.001 | |
CD20 PT † p = 0.018 * | int vs. low | 0.24 | 0.09–0.66 | 0.005 |
high vs. low | 0.70 | 0.29–1.67 | 0.420 | |
Ratios between densities of nucleated profiles of TIL (QA) in two ROIs | ||||
CD3 inn M/out M ǂ | above vs. under median (0.361) | 0.35 | 0.15–0.81 | 0.015 |
CD3 TC/out M ǂ | above vs. under median (0.201) | 0.45 | 0.21–1.03 | 0.058 |
CD3 TC/PT ǂ | above vs. under median (0.219) | 0.48 | 0.21–1.13 | 0.093 |
CD8 TC/PT ǂ | above vs. under median (0.161) | 0.48 | 0.20–1.12 | 0.091 |
CD20 inn M/out M ǂ | above vs. under median (0.113) | 0.26 | 0.11–0.62 | 0.002 |
CD20 TC/out M ǂ | above vs. under median (0.051) | 0.21 | 0.09–0.51 | 0.001 |
CD20 TC/PT ǂ | above vs. under median (0.049) | 0.28 | 0.12–0.66 | 0.004 |
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Trailin, A.; Červenková, L.; Ambrozkiewicz, F.; Ali, E.; Kasi, P.; Pálek, R.; Hošek, P.; Třeška, V.; Daum, O.; Tonar, Z.; et al. T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis. Cancers 2022, 14, 604. https://doi.org/10.3390/cancers14030604
Trailin A, Červenková L, Ambrozkiewicz F, Ali E, Kasi P, Pálek R, Hošek P, Třeška V, Daum O, Tonar Z, et al. T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis. Cancers. 2022; 14(3):604. https://doi.org/10.3390/cancers14030604
Chicago/Turabian StyleTrailin, Andriy, Lenka Červenková, Filip Ambrozkiewicz, Esraa Ali, Phanindra Kasi, Richard Pálek, Petr Hošek, Vladislav Třeška, Ondrej Daum, Zbyněk Tonar, and et al. 2022. "T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis" Cancers 14, no. 3: 604. https://doi.org/10.3390/cancers14030604