Table 2.
Univariable and multivariable Cox regression models for colorectal cancer-specific and overall survival according to the total, PD-L1+, and PD-L1− macrophage densities in the tumour centre and the invasive margin.
| No. of cases | Colorectal cancer-specific survival | Overall survival | |||||
|---|---|---|---|---|---|---|---|
| No. of events | Univariable HR (95% CI) |
Multivariable HR (95% CI) |
No. of events | Univariable HR (95% CI) |
Multivariable HR (95% CI) |
||
| Tumour centre | |||||||
| Macrophage density | |||||||
| Q1 | 228 | 64 | 1 (referent) | 1 (referent) | 116 | 1 (referent) | 1 (referent) |
| Q2 | 228 | 56 | 0.85 (0.59–1.21) | 0.81 (0.56–1.18) | 109 | 0.93 (0.71–1.21) | 0.92 (0.70–1.20) |
| Q3 | 227 | 63 | 0.97 (0.69–1.38) | 0.84 (0.59–1.20) | 107 | 0.93 (0.72–1.21) | 0.84 (0.64–1.10) |
| Q4 | 227 | 59 | 0.93 (0.65–1.32) | 0.80 (0.56–1.16) | 117 | 1.03 (0.80–1.33) | 0.84 (0.65–1.10) |
| Ptrend | 0.87 | 0.29 | 0.81 | 0.17 | |||
| PD-L1+ macrophage density | |||||||
| Q1 | 228 | 83 | 1 (referent) | 1 (referent) | 134 | 1 (referent) | 1 (referent) |
| Q2 | 228 | 61 | 0.68 (0.49–0.94) | 0.81 (0.57–1.13) | 106 | 0.72 (0.56–0.93) | 0.82 (0.64–1.07) |
| Q3 | 227 | 54 | 0.59 (0.42–0.83) | 0.75 (0.53–1.06) | 102 | 0.68 (0.53–0.88) | 0.73 (0.56–0.95) |
| Q4 | 227 | 44 | 0.47 (0.33–0.69) | 0.63 (0.43–0.93) | 107 | 0.70 (0.54–0.90) | 0.72 (0.55–0.94) |
| Ptrend | <0.0001 | 0.015 | 0.0050 | 0.011 | |||
| PD-L1– macrophage density | |||||||
| Q1 | 228 | 59 | 1 (referent) | 1 (referent) | 110 | 1 (referent) | 1 (referent) |
| Q2 | 228 | 52 | 0.86 (0.59–1.25) | 0.75 (0.51–1.09) | 111 | 1.01 (0.77–1.31) | 0.93 (0.71–1.22) |
| Q3 | 227 | 58 | 0.97 (0.68–1.39) | 0.88 (0.61–1.27) | 108 | 0.99 (0.73–1.29) | 0.93 (0.71–1.21) |
| Q4 | 227 | 73 | 1.31 (0.93–1.85) | 0.85 (0.60–1.21) | 120 | 1.18 (0.91–1.53) | 0.88 (0.67–1.14) |
| Ptrend | 0.085 | 0.62 | 0.25 | 0.35 | |||
| Invasive margin | |||||||
| Macrophage density | |||||||
| Q1 | 228 | 67 | 1 (referent) | 1 (referent) | 113 | 1 (referent) | 1 (referent) |
| Q2 | 228 | 62 | 0.94 (0.66–1.32) | 1.16 (0.81–1.66) | 118 | 1.07 (0.83–1.39) | 1.19 (0.91–1.56) |
| Q3 | 227 | 47 | 0.67 (0.46–0.97) | 0.92 (0.62–1.36) | 100 | 0.84 (0.64–1.09) | 0.98 (0.74–1.28) |
| Q4 | 227 | 66 | 0.99 (0.70–1.39) | 0.93 (0.66–1.32) | 118 | 1.05 (0.81–1.36) | 0.98 (0.76–1.28) |
| Ptrend | 0.54 | 0.46 | 0.83 | 0.57 | |||
| PD-L1+ macrophage density | |||||||
| Q1 | 228 | 92 | 1 (referent) | 1 (referent) | 136 | 1 (referent) | 1 (referent) |
| Q2 | 228 | 71 | 0.75 (0.55–1.02) | 1.07 (0.78–1.48) | 116 | 0.82 (0.64–1.06) | 1.02 (0.79–1.32) |
| Q3 | 227 | 43 | 0.43 (0.30–0.61) | 0.68 (0.47–0.99) | 97 | 0.64 (0.50–0.83) | 0.85 (0.65–1.12) |
| Q4 | 227 | 36 | 0.34 (0.23–0.50) | 0.52 (0.34–0.78) | 100 | 0.62 (0.48–0.80) | 0.69 (0.52–0.91) |
| Ptrend | <0.0001 | 0.0004 | <0.0001 | 0.0053 | |||
| PD-L1– macrophage density | |||||||
| Q1 | 228 | 55 | 1 (referent) | 1 (referent) | 113 | 1 (referent) | 1 (referent) |
| Q2 | 228 | 58 | 1.08 (0.74–1.56) | 1.33 (0.91–1.94) | 108 | 0.98 (0.75–1.28) | 1.08 (0.83–1.42) |
| Q3 | 227 | 50 | 0.88 (0.60–1.29) | 1.02 (0.69–1.50) | 101 | 0.86 (0.66–1.13) | 0.95 (0.72–1.25) |
| Q4 | 227 | 79 | 1.53 (1.08–2.16) | 1.36 (0.96–1.92) | 127 | 1.21 (0.94–1.56) | 1.13 (0.88–1.46) |
| Ptrend | 0.038 | 0.21 | 0.27 | 0.52 | |||
The densities were divided into ordinal quartile categories from low (Q1) to high (Q4).
Multivariable Cox proportional hazards regression models were adjusted for sex (male, female), age (<65, 65–75, >75), year of operation (2000–2005, 2006–2010, 2011–2015), tumour location (proximal colon, distal colon, rectum), stage (I–II, III, IV), tumour grade (well/moderately differentiated, poorly differentiated), lymphovascular invasion (negative, positive), MMR status (proficient, deficient), and BRAF status (wild-type, mutant).
Ptrend values were calculated by using the four categories of immune cell densities as continuous variables in univariable and multivariable Cox proportional hazard regression models.
CI confidence interval, HR hazard ratio.