Table 7.
The association of TAMs with the effect of chemotherapy in patients.
| Cohort of patient | Method of detection | The type and scheme of chemotherapy (adjuvant, neoadjuvant) | The amount of TAMs in chemotherapy-treated tumors | Correlation of TAM with the effect of chemotherapy | Reference |
|---|---|---|---|---|---|
| 311 breast cancer patients (Sweden) | Flow cytometry, IHC | Neoadjuvant (PTX and FU-doxorubicin-cyclophosphamide) | fivefold increase of CD45+CD11b+CD14+ macrophage percentage of total cells is found in NAC-treated patients compared to non-treated patients | CD68 high/CD8low ratio is associated with almost fourfold decreased pCR rate compared to cases with CD68low/CD8high ratio (7 vs. 27%) | (72) |
| 7 breast cancer patients (USA) | IHC | Neoadjuvant (paclitaxel-based) | Increased amount of CD68+ TAMs in tumor post NAC treatment compared to pre-treatment biopsy | Not studied | (95) |
| 33 breast cancer patients (UK) | IHC | Neoadjuvant (capecitabine plus docetaxel preceded by adriamycin and cyclophosphamide) | Not studied | High CD163+ infiltration (defined as grades 3 and 4) in primary tumor and ALNs are associated with pCR following NAC | (98) |
| 40 breast cancer patients (Russia) | Real-time qPCR | Neoadjuvant (PTX- or taxotere-based) |
Not studied | sixfold increase of YKL-39 expression levels after NAC correlates with distant metastasis and poor response to NAC | (17) |
| 123 metastatic CRC patients (Turkey) | IHC | Adjuvant (bevacizumab plus OXP-based or irinotecan-based chemotherapy) | Not studied | Low CD68+ TAM infiltration (scored as <50% staining of stromal cells) is associated with almost twofold longer OS (26.7 ± 8.8 vs. 14.1 ± 1.7 months) and 1.5-fold longer RFS (9.3 ± 1.8 vs. 6.5 ± 1.2 months) after chemotherapy compared to patients with high CD68+ TAM infiltration | (140) |
| 208 stage III CRC patients (Italy) | IHC | Adjuvant (5-FU) | Not studied | Increase of CD68+ TAM immune-reactive area above 8% in primary tumor is associated with increased DFS rate by 30% in 5-FU treated patients with stage III | (141) |
| 521 stage II colon cancer patients (China) | TMA | Adjuvant (FU-based) | Not studied | High CD206+ TAM amount (≥74 cells per ×200 HPF) and increase of CD206/CD68 ratio (above 0.77) correlate with decreased DFS and OS rates after postoperative FU-based therapy by 20% and 30-40%, respectively. | (124) |
| 163 stage II/III NSCLC patients (USA) | Multiplex IF | Neoadjuvant (platinum-based) | twofold increase of CD68+ TAM median density in NAC-treated compared to untreated patients (609.36 vs. 298.8 cells/mm2) | Increase of epithelial and stromal CD68+ TAM densities above the medians (17 and 25 cells/mm2, respectively, under ×200) correlate with increased OS rate by almost 20% in patients who received NCT | (186) |
| 27 stage IIIA NSCLC patients (China) | IHC (manually) | Neoadjuvant (cisplatin/docetaxel) | Not studied | Decrease of CD68+ TAM amount below the median (<222 cells per HPF ×200) is associated with threefold longer DFS (median=16.3 vs. 5.3 months in high CD68+ TAMs). High islet/stromal CD68+ TAM ratio (>1.33) correlates with almost fourfold longer DFS (median = 20.7 vs. 5.5 months) and longer OS (unreached vs. 34.8 months) compared to low ratio | (187) |
| 140 ovarian cancer patients (Italy) | Flow cytometry | Adjuvant (cisplatin/carboplatin + Taxol + bevacizumab) | twofold increase of M1/M2 ratio is found in platinum-sensitive tumors compared to platinum-resistant tumors (2.6 ± 1.1 vs. 0.7 ± 0.2). | High M1/M2 ratio (≥1.4) is associated with almost twofold longer OS (34 vs. 18 months) and almost threefold longer PFS (24 vs. 9 months) compared to those with low M1/M2 ratio | (210) |
ALN, axillary lymph node; CRC, colorectal cancer; DFS, disease-free survival; DSS, disease-specific survival; FU, fluorouracile; HPF, high-power field; IF, immunofluorescence; IHC, immunohistochemistry; LN, lymph node; NAC, neoadjuvant chemotherapy; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival; pCR, pathological complete response; RFS, recurrence-free survival; TAMs, tumor-associated macrophages; TMA, tissue microarray.