Correlation Between Tumor-Associated Macrophage and Immune Checkpoint Molecule Expression and Its Prognostic Significance in Cutaneous Melanoma
Abstract
:1. Introduction
2. Experimental Section
2.1. Study Design
2.2. Histopathological Analysis and Immunohistochemistry
2.3. Statistical Analyses
2.4. Variables of Interest
3. Results
3.1. Correlation between CD163, PD-1, and LAG-3 Expression in Melanoma Tissue
3.2. Expression of CD163, PD-1, LAG-3, and Their Association With Clinicopathological Features
3.3. Prognostic Significance of CD163, PD-1, and LAG-3 Expression
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Total | CD163High | CD163High PD-1High | CD163High LAG-3High | |||||||
---|---|---|---|---|---|---|---|---|---|---|
n = 102 | No (n = 55) | Yes (n = 47) | p-value | No (n = 70) | Yes (n = 32) | p-value | No (n = 70) | Yes (n = 32) | p-value | |
Age (years) | 0.455 | 0.662 | 0.624 | |||||||
Range | 25–89 | 25–80 | 31–89 | 25–89 | 31–86 | 25–89 | 31–82 | |||
Mean | 61.8 | 60.8 | 62.1 | 61.4 | 62.0 | 61.3 | 62.4 | |||
Sex | 0.769 | 0.705 | 0.419 | |||||||
Male | 57 | 30 (54.5) | 27 (57.4) | 40 (57.1) | 17 (53.1) | 41 (58.6) | 16 (50.0) | |||
Female | 45 | 25 (45.5) | 20 (42.6) | 30 (42.9) | 15 (46.9) | 29 (41.4) | 16 (50.0) | |||
Breslow thickness, mm | 0.001 * | 0.001 * | 0.011 * | |||||||
≤1 (T1) | 15/55 (27.2) | 6/47 (12.8) | T1 or T2 | T1 or T2 | T1 or T2 | T1 or T2 | ||||
>1 to ≤2 (T2) | 24/55 (43.6) | 12/47 (25.5) | 47/70 (67.1) | 10/32 (31.3) | 45/70 (64.3) | 12/32 (37.5) | ||||
>2 to ≤4 (T3) | 10/55 (18.2) | 16/47 (34.0) | T3 or T4 | T3 or T4 | T3 or T4 | T3 or T4 | ||||
>4 (T4) | 6/55 (10.9) | 13/47 (27.7) | 23/70 (32.9) | 22/32 (68.8) | 25/70 (35.7) | 20/32 (62.5) | ||||
Ulceration | 0.591 | 0.659 | 0.173 | |||||||
No | 70 | 39/55 (70.9) | 31/47 (66.0) | 49/70 (70.0) | 21/32 (65.6) | 51/70 (72.9) | 19/32 (59.4) | |||
Yes | 32 | 16/55 (29.1) | 16/47 (34.0) | 21/70 (30.0) | 11/32 (34.4) | 19/70 (27.1) | 13/32 (40.6) | |||
Vertical growth phase | 0.001 * | <0.001 * | <0.001 * | |||||||
No | 61 | 41/55 (74.5) | 20/47 (42.6) | 51/70 (72.9) | 10/32 (31.3) | 50/70 (71.4) | 11/32 (34.4) | |||
Yes | 41 | 14/55 (25.5) | 27/47 (57.4) | 19/70 (27.1) | 22/32 (68.8) | 20/70 (28.6) | 21/32 (65.6) | |||
Lymph node involvement | 0.005 * | 0.033 * | 0.008 * | |||||||
No | 80 | 49/55 (89.1) | 31/47 (66.0) | 59/70 (84.3) | 21/32 (65.6) | 60/70 (85.7) | 20/32 (62.5) | |||
Yes | 22 | 6/55 (10.9) | 16/47 (34.0) | 11/70 (15.7) | 11/32 (34.4) | 10/70 (14.3) | 12/32 (37.5) | |||
Visceral involvement | 0.087 | 0.048 * | 0.237 | |||||||
No | 94 | 53/55 (96.4) | 41/47 (87.2) | 67/70 (95.7) | 27/32 (84.4) | 66/70 (94.3) | 28/32 (87.5) | |||
Yes | 8 | 2/55 (3.6) | 6/47 (12.8) | 3/70 (4.3) | 5/32 (15.6) | 4/70 (5.7) | 4/32 (12.5) | |||
AJCC stage | 0.012 * | 0.028 * | 0.007 * | |||||||
I/II | 75 | 46/55 (83.6) | 29/47 (61.7) | 56/70 (80.0) | 19/32 (59.4) | 57/70 (81.4) | 18/32 (56.3) | |||
III/IV | 27 | 9/55 (16.4) | 18/47 (38.3) | 14/70 (20.0) | 13/32 (40.6) | 13/70 (18.6) | 14/32 (43.8) |
PD-1 Expression, n (%) | LAG-3 Expression, n (%) | |||||
---|---|---|---|---|---|---|
Low Expression (n = 49) | High Expression (n = 53) | p-Value | Low Expression (n = 58) | High Expression (n = 44) | p-Value | |
CD163 expression | 0.003 * | <0.001 * | ||||
Low expression (n = 55) | 34/49 (69.4) | 21/53 (39.6) | 43/58 (74.1) | 12/44 (27.3) | ||
High expression (n = 47) | 15/49 (30.6) | 32/53 (60.4) | 15/58 (25.9) | 32/44 (72.7) |
Mean OS (95% CI) (Months) | Mean PFS (95% CI) (Months) | |
---|---|---|
A) CD163lowPD-1low expression (n = 34) | 70.94 (61.78–80.10) | 51.48 (43.41–59.55) |
B) Either CD163lowPD-1high or CD163highPD-1low expression (n = 36) | 68.17 (57.36–78.98) | 50.46 (39.54–61.39) |
C) CD163highPD-1high expression (n = 32) | 57.57 (48.49–66.66) | 37.06 (32.24–41.87) |
D) CD163lowLAG-3low expression (n = 44) | 68.53 (60.20–76.85) | 50.19 (42.83–57.57) |
E) Either CD163lowLAG-3high or CD163highLAG-3low expression (n = 26) | 70.35 (57.80–82.89) | 50.93 (38.74–63.12) |
F) CD163highLAG-3high expression (n = 32) | 57.57 (48.49–66.66) | 36.89 (32.06–41.72) |
Overall (n = 102) | 66.86 (60.67–73.05) | 48.39 (42.26–54.53) |
p-value | ||
A, B, C separately | 0.036 *,§ | 0.026 *,§ |
C versus. others | 0.037 *,§§ | 0.031 *,§§ |
D, E, F separately | 0.064 ǂ | 0.044 *,ǂ |
F versus. others | 0.037 *,ǂǂ | 0.027 *,ǂǂ |
Univariate analysis | ||||||
---|---|---|---|---|---|---|
OS | PFS | |||||
Covariate | HR | 95% CI | p Value | HR | 95% CI | p Value |
Age (years) | ||||||
<60 vs. ≥60 | 0.92 | 0.68–2.93 | 0.328 | 1.10 | 0.68–1.78 | 0.624 |
Sex | ||||||
Female vs. Male | 1.84 | 0.67–3.28 | 0.412 | 1.28 | 0.79–4.57 | 0.492 |
AJCC stage | ||||||
Early vs. Advanced | 2.41 | 1.24–4.28 | 0.023 * | 2.19 | 1.14–5.37 | 0.045 * |
Involvement of LN | ||||||
Yes vs. No | 1.69 | 1.10–5.63 | 0.037 * | 1.13 | 1.16–5.74 | 0.041 * |
Amelanosis | ||||||
Yes vs. No | 0.69 | 0.23–4.69 | 0.333 | 0.71 | 0.29–5.19 | 0.572 |
Breslow thickness | ||||||
T1 | 0.75 | 0.35–0.82 | 0.027 * | 0.52 | 0.31–0.81 | 0.031 * |
T2 | 0.82 | 0.05–1.18 | 0.141 | 0.86 | 0.23–1.11 | 0.062 |
T3 | 1.88 | 1.16–5.23 | 0.029 * | 1.52 | 1.14–6.32 | 0.041 * |
T4 | 2.41 | 1.11-4.82 | 0.018 * | 1.99 | 1.19–5.81 | 0.039 * |
CD163 expression | ||||||
Yes vs. No | 2.62 | 1.39–4.88 | 0.033* | 2.71 | 1.13–4.16 | 0.159 |
LAG-3 expression | ||||||
High vs. Low | 2.11 | 1.21–5.20 | 0.037* | 2.07 | 1.13–5.31 | 0.041 * |
PD-1 expression | ||||||
High vs. Low | 1.09 | 0.59–4.75 | 0.421 | 1.13 | 0.85–4.92 | 0.280 |
CD163highPD-1high | 2.31 | 1.21–5.11 | 0.029* | 1.88 | 1.07–5.09 | 0.043 * |
CD163highLAG-3high | 2.03 | 1.18–5.44 | 0.032 * | 2.08 | 1.14–5.25 | 0.038 * |
Multivariate analysis | ||||||
AJCC stage | ||||||
Early vs. Advanced | 1.89 | 1.21–4.59 | 0.042 * | 1.87 | 1.11–4.21 | 0.051 |
Involvement of LN | ||||||
Yes vs. No | 1.12 | 0.82–4.19 | 0.156 | 1.17 | 0.65–3.84 | 0.147 |
Breslow thickness | ||||||
T1 | 0.88 | 0.43–0.91 | 0.043 * | 0.92 | 0.55–0.98 | 0.047 * |
T2 | 0.89 | 0.27–1.47 | 0.117 | 0.84 | 0.33–1.61 | 0.215 |
T3 | 1.16 | 1.08–5.14 | 0.088 | 1.21 | 1.03–4.22 | 0.174 |
T4 | 1.89 | 0.041 * | 1.61 | 1.10-4.87 | 0.063 | |
CD163 expression | ||||||
High vs. Low | 2.38 | 1.16–4.74 | 0.040 * | 2.19 | 1.06–5.08 | 0.188 |
LAG-3 expression | ||||||
High vs. Low | 1.99 | 1.19–5.44 | 0.044 * | 1.87 | 1.10–5.01 | 0.061 |
CD163highPD-1high | 2.08 | 1.14–5.57 | 0.042 * | 1.76 | 1.08–5.46 | 0.066 |
CD163highLAG-3high | 1.88 | 1.16–5.87 | 0.044 * | 1.54 | 1.07–5.13 | 0.046 * |
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Kim, Y.J.; Won, C.H.; Lee, M.W.; Choi, J.H.; Chang, S.E.; Lee, W.J. Correlation Between Tumor-Associated Macrophage and Immune Checkpoint Molecule Expression and Its Prognostic Significance in Cutaneous Melanoma. J. Clin. Med. 2020, 9, 2500. https://doi.org/10.3390/jcm9082500
Kim YJ, Won CH, Lee MW, Choi JH, Chang SE, Lee WJ. Correlation Between Tumor-Associated Macrophage and Immune Checkpoint Molecule Expression and Its Prognostic Significance in Cutaneous Melanoma. Journal of Clinical Medicine. 2020; 9(8):2500. https://doi.org/10.3390/jcm9082500
Chicago/Turabian StyleKim, Young Jae, Chong Hyun Won, Mi Woo Lee, Jee Ho Choi, Sung Eun Chang, and Woo Jin Lee. 2020. "Correlation Between Tumor-Associated Macrophage and Immune Checkpoint Molecule Expression and Its Prognostic Significance in Cutaneous Melanoma" Journal of Clinical Medicine 9, no. 8: 2500. https://doi.org/10.3390/jcm9082500