Table 3. Inflammatory cell populations and cytokine expression in inflammatory MSS, non-inflammatory MSS, and MSI colorectal cancers.
| Group 1 (n = 29) | Group 2 (n = 33) | Group 1 vs 2 | Group 3 (n = 48) | Group 3 vs 1 | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Marker | Inflammatory MSS CRC(1) | Non-Inflammatory MSS CRC | MSI CRC | |||||||||||||||||
| Mean | SEM | Median | Range | Mean | SEM | Median | Range | Ratio | p | Mean | SEM | Median | Range | Ratio | p | |||||
| CD3 ct | 882 | 612 | 701 | [65–2491] | 685 | 798 | 451 | [53–3673] | 1.29 | 0.044 | 1335 | 1320 | 905 | [13–5604] | 1.51 | 0.391 | ||||
| CD45RO ct | 977 | 787 | 705 | [64–2788] | 625 | 667 | 521 | [0–3362] | 1.56 | 0.055 | 1462 | 1031 | 1359 | [78–4595] | 1.49 | 0.031 | ||||
| CD68 im | 779 | 737 | 618 | [50–3678] | 601 | 568 | 469 | [20–2669] | 1.29 | 0.241 | 908 | 579 | 816 | [46–2022] | 1.17 | 0.188 | ||||
| CD68 ct | 364 | 276 | 328 | [14–1198] | 317 | 296 | 249 | [20–1274] | 1.15 | 0.378 | 626 | 364 | 596 | [43–1464] | 1.72 | 0.002 | ||||
| FoxP3 ct | 254 | 155 | 223 | [5–534] | 352 | 285 | 255 | [54–1162] | 0.72 | 0.378 | 250 | 183 | 206 | [15–820] | 0.98 | 0.701 | ||||
| CD8 ct | 303 | 420 | 155 | [5–1956] | 225 | 272 | 148 | [7–1057] | 1.35 | 0.459 | 717 | 724 | 505 | [31–2916] | 2.36 | 0.002 | ||||
| CD45RO im | 2045 | 1525 | 1715 | [139–5965] | 2326 | 2651 | 1574 | [99–11293] | 0.88 | 0.553 | 2716 | 1620 | 2614 | [125–6462] | 1.33 | 0.083 | ||||
| T-bet ct | 105 | 121 | 60 | [0–533] | 124 | 159 | 53 | [9–664] | 0.85 | 0.554 | 453 | 492 | 233 | [4–2053] | 4.30 | < 0.0001 | ||||
| FoxP3 im | 326 | 321 | 214 | [53–1508] | 383 | 531 | 177 | [0–2568] | 0.85 | 0.603 | 343 | 303 | 259 | [0–1159] | 1.05 | 0.761 | ||||
| CD8 im | 492 | 460 | 345 | [40–1806] | 579 | 751 | 268 | [18–3445] | 0.85 | 0.707 | 837 | 629 | 672 | [57–3154] | 1.70 | 0.006 | ||||
| CD3 im | 1041 | 936 | 761 | [152–3805] | 1308 | 1621 | 863 | [44–8474] | 0.79 | 0.789 | 1573 | 1017 | 1363 | [80–4059] | 1.51 | 0.013 | ||||
| T-bet im | 61 | 61 | 38 | [5–226] | 67 | 84 | 36 | [0–388] | 0.91 | 0.905 | 115 | 93 | 109 | [3–386] | 1.89 | 0.005 | ||||
| IL-16 | 7.14 | 3.84 | 6.48 | [1.75–14.05] | 11.63 | 10.02 | 10.54 | [2.08–53.59] | 0.61 | 0.059 | 14.90 | 14.89 | 12.10 | [0–87.05] | 2.09 | 0.002 | ||||
| IL-1ra | 56.38 | 90.45 | 27.83 | [7–464.13] | 102.11 | 132.94 | 44.21 | [.27–506.35] | 0.55 | 0.080 | 105.98 | 123.77 | 58.83 | [5.6–567.4] | 1.88 | 0.007 | ||||
| CCL5 | 0.29 | 0.57 | 0.12 | [0–2.37] | 0.49 | 0.96 | 0.15 | [0–4.29] | 0.59 | 0.438 | 5.16 | 18.13 | 1.37 | [0–125.92] | 17.79 | < 0.0001 | ||||
| CXCL8 | 12.27 | 24.75 | 2.79 | [0–114.29] | 16.69 | 50.25 | 1.51 | [0–284.63] | 0.74 | 0.494 | 77.05 | 149.22 | 12.70 | [.01–507.6] | 6.28 | < 0.0001 | ||||
| CXCL9 | 6.92 | 8.76 | 2.66 | [0.16–29.43] | 5.52 | 8.86 | 3.73 | [0–49.90] | 1.25 | 0.568 | 28.51 | 35.39 | 14.16 | [0–154.09] | 4.12 | < 0.0001 | ||||
| IL-1β | 3.43 | 12.71 | 0.09 | [0–68.39] | 1.2 | 2.48 | 0.15 | [0–10.58] | 2.86 | 0.577 | 5.13 | 8.86 | 1.78 | [0–41.93] | 1.50 | < 0.0001 | ||||
| CXCL10 | 6.44 | 9.98 | 1.85 | [0–44.67] | 5.31 | 8.31 | 1.54 | [0–34.12] | 1.21 | 0.843 | 61.36 | 238.43 | 8.50 | [0–1652.31] | 9.53 | 0.003 | ||||
| MIF | 107.45 | 57.42 | 102.78 | [50.73–319.81] | 105.96 | 50.97 | 87.37 | [47.68–226.69] | 1.01 | 0.927 | 89.23 | 60.19 | 76.16 | [0–350.63] | 0.83 | 0.084 | ||||
| CXCL1 | 1.77 | 2.51 | 0.89 | [0–12.89] | 1.99 | 2.67 | 1.00 | [0–12.80] | 0.89 | 0.978 | 2.84 | 3.58 | 1.40 | [0–18.59] | 1.60 | 0.057 | ||||
Based on the presence of a strong lymphocytic infiltration and/or Crohn’s-like lymphocytic reaction. The intratumoral (ct) and peritumoral (im) densities of CD3, CD8, T-Bet, CD45RO, FoxP3, and CD68 immunoreactive cells were assessed by image analysis of tissue microarray spots and expressed as number of cells/mm2. The amount of each factor was quantified using two multiplex assays and expressed as pg/mL for 25 µg of total protein extracted from MSS or MSI tumor samples containing at least 50% tumor cells. Data were compared with a non-parametric Mann-Whitney test. Abbreviations: CRC, colorectal cancer; MSI, microsatellite instable; MSS, microsatellite stable.