TABLE 1.
Landmark studies indicating the value of different cell populations in predicting CRC prognosis.
| Cell population | Author | Cancer location | TNM stage | Sample size | Main results |
|---|---|---|---|---|---|
| CAF | Akishima-Fukasawa et al. (131) | I–III | 110 | PGP9.5 expression is an independent prognostic factor for overall and recurrence-free survival. | |
| CAF | Glentis et al. (132) | CRC and adenoma | Not defined | 40 | CAFs actively assist cancer cells to breach the basement membrane. |
| CAF | Ren et al. (133) | CRC | Not defined | not defined | CAFs promote the stemness and chemoresistance of CRC by transferring exosomal H19. |
| CAF | Zhang et al. (134) | CRC | Not defined | not defined | Colorectal-cancer-CAFs-derived HGF induced up-regulation of CD44 which mediated adhesion of CRC cells to endothelial cells, and subsequently resulted in enhancement of metastasis of CRC. |
| CAF | Miyazaki et al. (135) | CRC and breast cancer | Not defined | not defined | The direct interaction with CAFs, as well as environmental cytokines, contributes to the collective invasion of cancers. |
| CAF | Unterleuthner et al. (136) | CRC | Not defined | not defined | WNT2 has a pivotal role in sustaining an activated CAF phenotype, which is associated with the maintenance of a pro-angiogenic secretome and contributes to elevated tumor angiogenesis in CRC. |
| DC | Bauer et al. (137) | CRC (MSI-H and MSS) | Not defined | 69 | Impaired DC maturation may contribute to local immune evasion in CRC. |
| DC | Gulubova et al. (138) | CRC | I - IV | 145 | The infiltration of colon cancer with DCs is related to tumor progression and patient prognosis, suggesting a central role of DCs in controlling local tumor immunity. |
| DC | Hu et al. (139) | CRC | not defined | 19 | Treatment with anti-PD-L1 may promote the maturation of Dcs and enhance the functionality of DC1 subtype. |
| DC | Miller et al. (75) | CRC | III | 221 | PD-L1-expressing DC in the tumor microenvironment are associated with improved survival in stage III colon cancer and likely reflect an immunologically “hot” tumor microenvironment. |
| B cells | Berntsson et al. (140) | CRC | I–IV | 557 | Dense infiltration of CD20+ B-cells is an independent predictor of a favourable clinical outcome. |
| B cells | Edin et al. (141) | CRC | I–IV | 316 | There is a positive prognostic role of tumour-infiltrating CD20+ B lymphocytes in CRC patients. |
| B cells | Mullins et al. (142) | CRC and rectal cancer | III–IV | 25 | Tumor-infiltrating B cells can contribute to tumor control in a dula role of sole antigen-presentation and additionally anti-tumoral Ig-production. |
| B cells | Toor et al. (83) | CRC | I–IV | 50 | Decreased levels of B cells and selective IC-expressing CD8+ TILs are associated with tumor progression. MSI-H tumors could show favorable prognosis/improved response to cancer immunotherapy. |
| T cells | Li et al. (51) | CRC | I–IV | 356 | Higher expressions of PD-1 and PD-L1 correlates with a better prognosis in CRC patients. |
| T cells | Berntsson et al. (143) | CRC | I–IV | 557 | A high density of cytotoxic T cells is an independent prognostic factor in right-sided tumours and regulatory T cells predict longer survival only in patients with rectal tumours. |
| T cells | Digiacomo et al. (144) | BRAF-mCRC | IV | 59 | A simultaneous evaluation of MSI, CD8 T-cell content, and neuroendocrine markers could allow for the identification of subsets of BRAF-mCRC with a different prognosis and potential eligibility for specific treatments. |
| T cells | Glaire et al. (145) | CRC | II–III | 1804 | The prognostic value of intratumoral CD8+ cell infiltration in stage II/III CRC varies across tumour and nodal risk strata. |
| T cells | Fiegle et al. (12) | Mouse model of CRC | 25 | Dual CTLA- and PD-L1 blockade exert synergistic inhibitory effects on growth and metastasis of the orthotopic CT26 colon tumors by increasing CD8+ and CD4+ T cells. | |
| T cells | Kuwahara et al. (64) | CRC | I–IV | 342 | Intratumoral CD4+ T-cell density and combined CD4+ and FOXP3+ T-cell densities were stronger prognostic factors than other clinicopathological features. |
| T cells | Craig et al. (146) | CRC | II–IV | 1724 | Immune cold patients by assessment of CD3, CD4 and CD8 IHC are linked with difficult-to-treat, poor prognosis hypoxic biology, which may be potentially amenable to targeted therapy or monitoring for disease progression. |
| T cells | Noh et al. (48) | CRC | I–IV | 489 | Tumours with PD-L1-positive tumour cells and high-CD8 TIL is associated with the best prognosis, and show stronger CD8/PD-L1/Pd-1 signalling interaction compared to the other types. |
| T cells | Hartman et al. (147) | CRC | I–IV | 259 | The prognostic value of MMR protein deficiency is most likely attributed to increased tumor-associated CD8-positive T cells and that automated quantitative CD8 T-cell analysis is a better biomarker of patient prognosis. |
| T cells | Fuchs et al. (148) | CRC | I–IV | 1034 | ITWG systém for assessing TILs is a powerful predictor of all-cause survival in CRC independent of many prognostic factors and superior to the assessment of intraepithelial lymphocytes using a traditional system. |
| T cells | Lalos et al. (149) | CRC | I–IV | 613 | The combination of high CD8+ T-cell density and expression of SDF-1 represents an independent, favorable, prognostic condition in CRC, mostly in patients with stage III disease. |
| T cells | Al-Badran et al. (150) | CRC | I–III | 773 | Individual and combined high expression of TIM-3, LAG-3, and PD-1 on stromal immune cells are associated with better colorectal cancer prognosis. |