Table 1.
The association of tumor infiltrating lymphocytes with microsatellite stability status in colorectal cancer.
| Author | Markers | Sample size (dMMR-MSI-H | pMMR-MSI-L/MSS) | Disease stage | TILs feature |
|---|---|---|---|---|
| Liu et al. (42) | CD3, CD4, CD8, CD56 | 167/163 | I-IV | dMMR group displayed higher CD8 cells (p < 0.01). CD56+ cells CD4+ cell than pMMR group (both p < 0.05). |
| Flahec et al. (43) | CD3, CD4, CD8, CD20, CD68, FOXP3 | 35/34 | I-IV | dMMR tumors have more numerous intraepithelial (CD3+, CD8+, FOXP3+) and stromal (CD8+) lymphocytes |
| Michael-Robinson et al. (44) | CD3, CD8, CD20 | 32/70 | Duke’s stage A-D | TILs were most abundant in MSI-H colorectal cancers in which 23/32 (72%) scored as TILs positive. Only 5/40 (12.5%) MSS tumours and 9/30 (30%) MSI-L cancers were TILs positive (p < 0.0001). |
| Phillips et al. (45) | CD3, CD4, CD8 | 26/138 | NA | MSI-H tumours showed significantly higher counts for CD3+ and CD8+ cells, but no differences were found in CD4 counts. |
| Dolcetti et al. (46) | CD3, CD4, CD8, CD56 | 18/37 | Duke’s A-D | MSI cases carried significantly higher numbers of cytotoxic lymphocytes infiltrating within neoplastic epithelial structures (p < 0.001) |
| Mlecnik et al. (47) | CD8, CD20, CD68, IL-17, NKp46, CD45RO | 186/114 | I-IV | A significant increase in cytotoxic T cell, B cell in tumors from MSI patients. MSI tumors had higher densities of Th1. The MSS patients showed a significantly increased Th17 infiltration in the core and invasive margin of tumor (p < 0.05) |
| Smedt et al. (48) | CD3, CD4, CD8, CD20, CD68 | 29/27 | I-IV | An increased number of tumor-infiltrating cytotoxic T-lymphocytes (CD8+) in MSI compared with MSS tumors for both the tumor and peritumoral area. Quantification showed high numbers of intra-epithelial CD3+, CD4+, CD8+, CD20+ and CD68+ cells in MSI compared with MSS cancers (all p <= 0.01). |
| Nestarenkaite et al. (49) | CD8, CD20, CD68 | 39/48 | I-IV | The CD8+ densities within tumor-stroma interface zone (IZ) and the intratumoral densities were higher in MSI than in MSS tumors, whereas no differences in IZ and intratumoral CD20+ cell densities were observed comparing MSI and MSS tumors |
| Gouvello et al. (50) | IL-17 | 10/11 | I-IV | Higher tumoral expression of Foxp3, IL-17, IL1-beta, IL-6 and TGF-β was associated with the MSS phenotype, and the IL-17 T/TN (colon cancers/autologous normal colon mucosa) ratio was higher in MSS tissues than in MSI-H tissues. |
| Michel et al. (51) | CD3, CD8, FOXP3 | 37/33 | I-IV and NA | The elevated number of CD8+ lymphocytes found in MSI-H colorectal cancers is paralleled by an enhanced infiltration with CD8- FOXP3+ cells |
Th, T helper; Treg, regulatory T cell; dMMR-MSI-H, mismatch-repair-deficient and microsatellite instability-high; pMMR-MSI-L/MSS, mismatch-repair-proficient and microsatellite-stable or have low levels of microsatellite instability; TILs, tumor infiltrating lymphocytes.