Table 4.
Representative studies demonstrating the association of TAMs with tumor progression parameters in lung 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 |
|---|---|---|---|---|---|
| 68 NSCLC patients (China) | IHC (not specified) | Positive CD68+ expression correlates with higher TNM stage (III and IV) | Positive CD68+ expression correlates with the presence of LN metastases | Not studied | (165) |
| 160 NSCLC patients (Japan) | IHC (manually) | High stromal (>380/mm2 in ×400 HPF) and alveolar CD163+ TAM densities (>400/mm2) are indicative for increase of CRP level up to 2 times, increase of invasive size by 20–45%, poor differentiation and advanced stages (II and III) | 1,4-fold increase of stromal and alveolar CD163+ TAM densities is indicative for tumors with N1–N3 nodal status vs. cases without LN metastases | In early stages (0 and I), high stromal CD163+ TAM density correlates with reduced DFS rate by 20% and OS by 12%. In advanced stages (II and III), high alveolar CD163+ TAM density correlates with reduced DFS rate by 22% and OS by 17% |
(166) |
| 335 NSCLC patients (Danmark) | IHC (digital imaging scanning) | Not significant | twofold increase of median area fraction of CD163+ TAMs in tumor nest and 1.5-fold increase in tumor stroma are found in cases with N1/N2 nodal status vs. those without LN metastases | Not significant | (167) |
| 297 NSCLC patients (Japan) | IHC (digital imaging scanning) | Increase of stromal CD68+ and CD204+ TAM amounts above the medians (48 and 15, respectively, under ×200) positively correlates with Ib-IV stages and G2-G4 histological grade | High amount of CD68+ (>48) and CD204+ (>15) TAMs correlates with pleural invasion and LN metastasis | High amount of CD68+ (>48) and CD204+ (>15) TAMs in tumor stroma correlates with decreased DFS rates by 10% | (168) |
| 553 primary NSCLC patients (Norway). | Multiplexed-IHC in TMA (digital imaging scanning) | Increase of stromal HLA-DR+/CD68+ TAM amount >1.0 under ×200 is indicative for lower T stages (T1 and T2) | Not studied | High amount of intratumoral and stromal HLA-DR+/CD68+, CD204+ and CD68+ TAMs correlates with increased DSS rates (appr. by 10-20%) | (169) |
| 80 NSCLC patients (Lithuania) | IHC (manually) | High amount of CD163+TAMs is found in tumors with poor differentiation (median 118 per 10 HPFs under ×400) versus moderate and well differentiated (median 108) | High amount of stromal CD68+ TAMs is found in tumors with N1-N3 nodal status (median 77 per 10 HPFs under ×400) vs. cases without LN metastases (median 64) | High CD68+iNOS+ and low CD68+ CD163+ amount correlates with increased OS rates by almost 50% | (170) |
DFS, disease-free survival; DSS, disease-specific survival; CRP, C-reactive protein; HPF, high-power field; IF, immunofluorescence; IHC, immunohistochemistry; LN, lymph node; NSCLC, non-small lung cancer; TAMs, tumor-associated macrophages; OS, overall survival; RFS, recurrence-free survival; TMA, tissue microarray.