Table 3.
Representative studies demonstrating the association of TAMs with tumor progression parameters in colorectal cancer.
| Cohort of patients | Method of detection | TAM correlation with tumor growth and stage | TAM correlation with lymphatic and hematogenous metastasis | TAM correlation with survival | Reference |
|---|---|---|---|---|---|
| 210 patients with primary CRC (Bulgaria) | IHC (digital imaging scanning) | Amount of CD68+TAMs (per hot spot ×320) in invasive front is decreased by almost 25% in advanced III + IV stages (114.9 ± 91.9 vs. 150.2 ± 102.3 in I + II stages) | Amount of CD68+TAMs (per hot spot ×320) in invasive front is decreased by 17% in tumors with regional LN metastases (119.4 ± 96.5 vs. 143.3 ± 100.0 in cases with negative LN), and by 42% in tumors with distant metastases (150.4 ± 105.8 vs. 87.8 ± 54.3 in negative cases) | Increased amount of CD68+ TAMs above 48.6 cell/mm2 in tumor stroma and above 105.2 cell/mm2 in invasive front is associated with increased OS rates by 10 and 40%, respectively | (119) |
| 201 patients with primary CRC (Greece) | IHC in next-generation TMA (manually) | High amount of intraepithelial CD68+ TAMs (counted per hot spot ×400) predicts less tumor budding High amount of CD163+ TAMs (counted per hot spot ×400) is indicative for G1-2 grades |
High amount of CD68+ and CD163+ TAMs is associated with absence of LN metastasis | High amount of CD68+ TAMs correlates with better OS (increase by 40%) | (120) |
| 488 patients with colon and rectal cancer (Sweden) | IHC (manually) | High CD68+ infiltration (defined as grades 3 and 4 in hot spot ×200) at the invasive front is indicative for I+II stages and well-moderate grade | Not studied | High CD68+ infiltration (defined as grades 3 and 4 in hot spot ×200) at the invasive front correlates with increased DSS rate by 30% | (121) |
| 160 patients with stage IIIB and IV colon carcinoma (China) | IHC (manually) | Not significant | High CD68+ infiltration (defined as grades 3 and 4 in hot spot ×200) at the invasive front is associated with absence of hepatic metastasis | High CD68+ infiltration (defined as grades 3 and 4 in hot spot ×200) at the invasive front correlates with increased OS rate by 30% and liver-metastasis free survival rate - by 20% | (122) |
| 163 patients with rectal cancer (Sweden) | IHC in TMA (manually) | Not significant | Not studied | Presence of CD163+ TAMs in tumor tissue is associated with reduced OS and RFS rates by 40% | (123) |
| 81 patients with CRC (China) | IHC (manually using immunoreactive score) | Increase of CD163+ TAM expression above the median (measured semiquantitatively at ×400) is indicative of III TNM stage, poor tumor grade | High CD163+ expression positively correlates with lymphovascular invasion and N2-3 LN status | High CD163+ expression is associated with reduced OS rate by 30% and RFS by 20% | (114) |
| 521 and 314 patients with stage II CRC (China) | IHC in TMA (digital imaging scanning) | Increase of CD206/CD68 ratio ≥ 0.77 is indicative of poor differentiation and undifferentiation status and pathological T4 stage |
Increase of CD206/CD68 ratio ≥ 0.77 is associated with lymphatic/vascular invasion and perineural invasion |
Increase of CD206/CD68 ratio ≥ 0.77 correlates with reduced DFS rate by 40% and OS by 30% |
(124) |
| 159 patients with advanced colorectal cancer (stage IV) (Finland) | IHC (manually) | Not studied | Low amount of intratumoral stabilin-1+ TAMs (<10 cells per ×400 hotspot) correlates with low number of distant recurrences | High amount of peritumoral stabilin-1+ TAMs (≥10 cells per ×400 hotspot) correlates with longer DFS time (103 vs. 63 months in cases with low amount) at stages II and III, but correlates with reduced DSS rate by almost 2 times in stage IV patients | (125) |
CRC, colorectal cancer; DFS, disease-free survival; DSS, disease-specific survival; IF, immunofluorescence; IHC, immunohistochemistry; LN, lymph node; TAMs, tumor-associated macrophages; OS, overall survival; RFS, recurrence-free survival; TMA, tissue microarray.