Table 1 Tumor associated macrophages in situ
From: Identification and manipulation of tumor associated macrophages in human cancers
Organ | Cancer type | n1 | Method2 | Markers | Macrophage infiltrate? | Link to prognosis3 | Ref |
|---|---|---|---|---|---|---|---|
Lymphnode | Hodgkins lymphoma | 265 | TMA IHC | CD68 CD163 | Using a 5% of cells is positive cut-off; 80% is CD68+ cell positive and 64% is CD163+ | No link | 7 |
| Â | Hodgkins lymphoma | 130 and 166 | IHC | CD68 MMP11 | Using a 5% and 1% of cells is positive cut-off;72% is CD68+ cell positive and 41% positive for MMP-11 | High CD68+ MF or high MMP-11 expression correlates with poor disease specific survival | 40 |
| Â | Hodgkins lymphoma | 105 | TMA IHC | CD68 | 42% has high MF infiltration (> 0,82% of total cells is positive for CD68) | High infiltration correlates with higher age and poor survival (also in the younger patients) | 42 |
Colon | CRC | 17 | IHC | CCL2 CD68 IL-8 | Mean MF number in tumor 8/mm3, in stroma 44/mm3 and necrotic area´s 44/mm3 and all tumors are high IL-8 postive | Tumor cell produced CCL2 correlates to MF count and advanced disease stage | 8 |
| Â | CRC | 478 | IHC | CD68 | 76% has high MF infiltration at tumor front | High MF count at tumorfront associates with better prognosis | 16 |
| Â | CRC | 118 | IHC | CD68 MMP-2 MMP-9 | 47% has high MF numbers and this correlates with expression of MMP-2 and MMP-9 | Intratumoral TAM correlate with invasion, LN status and staging | 21 |
| Â | CRC | 40 | DIHC | CD68 S100 CD163 | In all samples MF infiltration, more in stroma than in tumor beds. Mean is 12/15 per high power field. | Significant better survival for patient with high DC count and trend for high CD163 count. | 29 |
| Â | CRC | 159 | IHC | CD68 Clever-1/Stabilin-1 CD206 CD3+ | 98% has peritumoral macrophages in 10 tested tumors all MF are CD206/Clever-1 dubbelpositive | High peritumoral CD68 better prognosis; low intratumoral M1/M2 ratio more recurrent disease | 52 |
| Â | CRC metastasis in liver | 15 | IHC | CD68 CD163 CXCL-10 CXCR-4 CXCL-12 Her1 Her4 HB-EGF | CD68, CXCL-10, CD163 positive cells are found in al lesions | -- | 35 |
Intestinal tract | GIST | 47 (19 metastatic) | FIHC | CD68 CD163 CD14 CD1a CD20 S100, HLA-DR CD3 CD8 FoxP3 CD33 | High infiltrate in primary lesion tumors (2,7%) and metastatic lesions (4,9%) of CD163+ macrophages. | Presence of M2 is correlated with FoxP3 positive infiltrate | 43 |
| Â | gastric cancer | 105 | IHC ZG | hypoxia CD68 CD34 VEGF MMP2 +9 | More macrophages in hypoxic area's | Hypoxia and more macrophages correlates with shorter survival | 34 |
Lung | NSCLC | 100 | DIHC | CD68 HLA-DR CD163 | Of CD68 positive MF 70% express CD163, 3% is positive for CD163 and HLA-DR | Patients with long survival have higher number of M1 type MF | 28 |
| Â | NSCLC | 50 | DIHC | CD68 IL-10 | 95% of IL-10 positive cells in advancing tumor margin is of MF origin | High IL-10 positive MF in advanced disease and therefore correlated to poor prognosis | 46 |
| Â | NSCLC | 40 | IHC | CD68 DR CD163 VEGF TNFa iNOS, | Less MF infiltrate in tumor islets of patient with shorter survival (all MF types) | More MF in tumor islets correlate with better prognosis | 32 |
| Â | NSCLC | 20 | IHC | CXCR-1,2,3 ,4,5 and CCL-1 | CXCR-3 is positively correlated with MF number as determined in (ohri ERJ 2009) | Higher CXCR-2, CXCR-3 and CCL-1 expression in patients with extended survival | 33 |
Mesothelioma | pleural mesothelioma | 52 (+ 7 flowcytometry) | IHC | CD68 CD163 CD206 CD124 | CD68+ MF comprised 27 % of tumor area, 7 tumors tested by flowcytometry; MF express high levels of M2 markers | High MF number in non-epithelial tumors is associated with bad prognosis | 10 |
Breast | breast CA | 110 + 106 | IHC | CD68 anti-PCNA (proliferation) | Double positive proliferating macrophages are found in most tumors | High number of proliferating macrohpages associated with decreased survival | 12 |
| Â | breast CA | 127 | IHC | CD68 CD163 MAC387 | Using a 25% surface area cut0off; 48% has high infiltration of CD163+ cells, MAC387 expression in 12% | High CD163 correlates with more distant disease recurrence | 38 |
Breast and Colon | primairy metastatic lesions | 49 breast and 12 colon metastasis | IHC | FCγRIIIa, FCγRII, CTSL1, CD163 | Signature in primary lesion is the same as in corresponding metastatic lymphenode | -- | 44 |
Ovarian and Peritoneum | ovarium carcinoma | Â | MS DIHC/FIHC | levels of eicosanoids (PGE2) and other related enzymes | High levels of eicosanoids in tumors, peritumoral CD163+ MF express COX and PGES | -- | 17 |
| Â | epithelial ovarian carcinoma | 40 (21 serous, 19 mucinous) | IHC | CD68 CD163 CD204 CSF-1 | M2 cells present in stomal compartment of all patients, MF number and CSF-1 increase with disease progression | High M2 correlates with disease stage | 22 |
| Â | ovarium CA | 60 +12 | FIHC DIHC Flow | B7-H4 HAM56 CD3 | 70% of intratumoral MF express B7-H4 | -- | 24 |
| Â | ovarium CA | 103 | DIHC | B7H4 HAM56 (CD4 FoxP3) | Higher expression of B7-H4 on macrophages in advanced stage and correlate with the presence of regulatory T cells. | High B7-H4 expression on MF correlates with poor survival | 25 |
Uterus | endometrioid carcinoma | 64 | IHC | CD163 CD31 HIF-1A | Only invasive tumors have high MF infiltration, more HIF1A and higher vessel density | In paired LN metastatic lesion same pattern for CD163 and CD31 is found | 14 |
| Â | endometrioid adeno CA | 61 | IHC | MMP-12 en CD68 | Higher MF and MMP-12 expression in more advanced disease | Higher MMP-12 and MF in advanced disease | 45 |
Cervix | CIN, HSIL, CxCa | 86 | IHC | CD68 | Number of MF correlates with disease progression | High MF number predicts disease progression | 18 |
Skin | stage 1/2 melanoma | 227 blood 190 tumors | IHC ELISA | CD68 CD163 and soluble CD163 | 67% has dense infiltration with CD163 cells at invasive front and stroma | High CD163 in tumor front or stroma correlates with poor survival | 20 |
| Â | metastatic melanoma | 6 | FIHC | CD45 CD68 CD163 CD209 CXCL-12 | 60% of perivascular TAM expres CXCL-12 | -- | 37 |
Prostate | first diagnostic screening; | 92 of which 30% has prostate ca | IHC | CD68 CD204 | Less CD204 positive cells is associated with development of prostate CA | -- | 31 |
| Â | needle biopsies prostate | 135 | IHC | CD204 | CD204 positive cells present in all samples | -- | 41 |
Eye | eye melanoma | 43 | FIH | CD68 CD163 | Most MF are double positive, more macrophages in monosomy of chromosome 3 | Less macrohpages is associated with better survival | 9 |
Kidney | renal cell carcinoma | 43 | DIH | CD209 CD14 CD163 | Most CD209+ cells were also CD14 and CD163+ | -- | 15 |
Liver | hepatocellular carcinoma | 63 | IHC | CD68 B7-H1 (PD-L1) | High B7-H1 expression on tumorcells if high macrophage infiltration (48% of patients) | -- | 13 |
| Â | intra-hepatic cholangiocarcinoma | 39 | IHC | CD68 CD163 CD34 FoxP3 | 50% of patients has high M2 infiltration and this correlates with vessel density and FoxP3+ numbers | High CD163+ correlates to poor disease free survival | 19 |
Brain | glioma | 79 | DIHC | CD68 CD163 CD204 M-CSF | Higher macrophage infiltration and shift towards M2 type in advanced stage | More CD163+CD204+ macrophages and high M-CSF in advanced stages | 23 |
Pancreas | pancreatic head cancer invasive ductal cancer | 76 | DIHC | CD68 CD163 CD204 | 42% shows high M2 infiltration perivasculair in invasive front | High M2 infiltration associated with LN metastasis | 26 |
Soft tissues | leiomyosarcoma | 76 gynecologic and 73 non- gynaecologic | TMA IHC | CD68 CD163 | 44% of patients has dense infiltrate with CD163+ cells | In non-gynecologic tumors, high CD163+ number correlate with poor prognosis | 27 |
Peripheral Lymphoma | angioimmunoblastic T cell lymphoma | 42 | DIHC | CD68 CD163 | Only invasive tumors have high MF infiltration, more HIF1A and higher vessel density | CD163/CD68 ratio correlates to overall survival | 30 |
Thyroid | anaplastic carcinoma | 27 | IHC | NOX-2 P22-phox CD68 CD163 | All tumors display a very dense network of TAM, 57% of tumor is TAM | -- | 11 |
| Â | thyroid cancer | well/poor/anaplastic 33/37/20 | IHC | CD68 CD163 | 27/54/95% has high CD 68 macrophage infiltrate thus more macrophage in advanced stage | -- | 36 |
Salivary gland | salivary gland | 35 | IHC | CD68 CD34 VEGFa | High infiltration with CD68 in 50% of patients | -- | 39 |