Optimum immunohistochemical procedures for analysis of macrophages in human and mouse formalin fixed paraffin-embedded tissue samples

Nakagawa, Terumasa; Ohnishi, Koji; Kosaki, Yui; Saito, Yoichi; Horlad, Hasita; Fujiwara, Yukio; Takeya, Motohiro; Komohara, Yoshihiro

doi:10.3960/jslrt.17017

Cited by 61 publications

(47 citation statements)

References 30 publications

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“…We previously found that there was a significant correlation between PD‐L1 expression in cancer cells and macrophage infiltration in the tumor microenvironment, and macrophage‐derived tumor necrosis factor‐α was revealed to induce PD‐L1 overexpression via NF‐κB signal activation in pancreatic cancer . In the present study, macrophage infiltration was also detected by Iba‐1 IHC as described previously . Because it was difficult to count the macrophage density adequately in the sections, we could not evaluate the correlation between PD‐L1/2 TPS and macrophages.…”

Section: Discussionmentioning

confidence: 57%

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

et al. 2019

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The percentage of programmed death ligand 1 (PD‐L1) positivity in cancer cells, named as the tumor proportion score, is considered to be a predictive biomarker for anti‐PD‐1/PD‐L1 therapy in lung cancer. PD‐L1 is expressed on not only cancer cells but also on immune cells, including macrophages. Although previous studies related to PD‐L1/2 expression in cancer tissues have been generally based on single immunohistochemistry (IHC), in the present study, we attempted to evaluate accurate PD‐L1/2 expression in cancer cells in lung adenocarcinoma cells using double IHC to also evaluate macrophages. Of the 231 patients, PD‐L1 expression was negative in 169 patients (73.2%), 1%‐49% positive in 47 patients (20.3%), and ≥50% positive in 15 patients (6.5%). Interestingly, PD‐L1 positivity was decreased when using double IHC compared with the estimation by single IHC. High PD‐L1 expression was associated with high‐grade cancer cells and in higher stage cancer. PD‐L2 was negative in 109 patients (47.2%), 1%‐49% positive in 50 patients (21.6%), and ≥50% positive in 72 patients (31.2%). The number of PD‐L2‐positive patients was increased in cases that had an epidermal growth factor receptor (EGFR) mutation and in lower stage cancer. Thirty‐five patients (15.2%) were positive for both PD‐L1 and PD‐L2, whereas 81 patients (35.1%) were negative for both PD‐L1 and PD‐L2. Log‐rank analysis showed that progression‐free survival and overall survival were significantly the longest in the PD‐L1‐negative and PD‐L2‐positive groups (P < .0001 and P = .0120). We observed lower PD‐L1 or PD‐L2 expression in lung adenocarcinoma than previously reported. Double IHC for macrophages may help clinicians to evaluate PD‐L1 or PD‐L2 expression specifically in cancer cells.

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Section: Discussionmentioning

confidence: 57%

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

et al. 2019

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“…Immunohistochemical analysis was performed essentially as described previously. 48 Antibodies used were as follows: anti-IL-34 (1D12; Abcam), anti-Iba-1 (#016-26461; Wako, Japan) and anti-CD163 (#10D6; Leica Biosystems, Nussloch, Germany).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Expression of IL‐34 correlates with macrophage infiltration and prognosis of diffuse large B‐cell lymphoma

et al. 2019

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Objectives Infiltration of macrophages through the tyrosine kinase receptor CSF1R is a poor prognosis factor in various solid tumors. Indeed, these tumors produce CSF1R ligand, macrophage colony‐stimulating factor (M‐CSF) or interleukin‐34 (IL‐34). However, the significance of these cytokines, particularly, the newly discovered IL‐34 in haematological malignancies, is not fully understood. We therefore analysed the role of IL‐34 in diffuse large B‐cell lymphoma (DLBCL), the most common subtype of malignant lymphoma. Methods We analysed formalin‐fixed paraffin‐embedded lymphoma tissues of 135 DLBCL patients for the expression of IL‐34 and the number of macrophages, and the survival of these patients. The expression of IL‐34 in DLBCL cell lines and the activity of IL‐34 to induce the migration of monocytic cells were also characterised. Results Several lymphoma tissues showed a clear IL‐34 signal, and such signal was detectable in 36% of patients. DLBCL cell lines also expressed IL‐34. Interestingly, the percentage of IL‐34+ patients in the activated B‐cell subtype was significantly higher than that in the germinal centre B‐cell subtype. More interestingly, IL‐34+ patients showed shorter survival periods and higher number of macrophages in lymphoma tissues. The recruitment of monocytes is likely the first step for the higher macrophage density in the IL‐34+ lymphoma tissues. Indeed, IL‐34 induced the migration of monocytic cells. Conclusion Our results raise the possibility that IL‐34 in lymphoma tissues of DLBCL patients recruits monocytes, leading to the higher number of macrophages in the tissues and poor prognosis of patients. IL‐34 may be an additional therapeutic target of DLBCL.

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“…TAM infiltration has been found to correlate with a poor prognosis in SCC . Of the several characteristic markers of macrophages, CD163 has been reported as a highly specialized marker of M2 monocyte‐derived alternative macrophages . Furthermore, CD163‐positive TAMs are chiefly associated with lymphatic vessel invasion and lymph node metastasis in OSCC via VEGF‐C expression …”

Section: Introductionmentioning

confidence: 99%

Macrophage CCL22 expression in the tumor microenvironment and implications for survival in patients with squamous cell carcinoma of the tongue

Kimura

Nanbu

Noguchi

et al. 2019

J Oral Pathology Medicine

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Background CCL22, mainly synthesized by monocyte‐derived alternative (M2) macrophages, belongs to the CC family of chemokines. CCR4, the receptor for CCL22, is expressed in regulatory T cells (Tregs) and Th2 cells. The Yamamoto‐Kohama (YK) mode of invasion has been associated with tumor prognosis. Herein, we investigated the role of CCL22 in the tumor microenvironment and its effect on the overall survival rate in patients with tongue squamous cell carcinoma (SCC). Methods Tumor sections obtained from 92 patients with tongue SCC were graded based on the mode of invasion according to the YK classification. The expressions of several markers (CCL22, CD8, and Ki‐67 by immunohistochemistry; CCR4 and FoxP3 by immunofluorescent staining) were evaluated. Student's t test and chi‐square tests were used to compare differences between numerical variables and groups, respectively. Survival curves were plotted according to the Kaplan‐Meier method and compared using a log‐rank test. Hazard ratios and 95% confidence intervals were estimated using univariate or multivariate Cox proportional hazard models. Results The expression of CCL22 was significantly correlated with YK classification, overall survival rate (P < 0.001), a decrease in the number of CD8‐positive cells, and an increase in the tumor Ki‐67 index. In addition, CCR4‐positive cells were observed around CCL22‐positive macrophages. Conclusion These findings indicate that the expression of CCL22 in the tumor microenvironment led to a deterioration in the prognosis of patients with tongue SCC by influencing the balance of M1‐ and M2‐like macrophages.

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Optimum immunohistochemical procedures for analysis of macrophages in human and mouse formalin fixed paraffin-embedded tissue samples

Cited by 61 publications

References 30 publications

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

Expression of IL‐34 correlates with macrophage infiltration and prognosis of diffuse large B‐cell lymphoma

Macrophage CCL22 expression in the tumor microenvironment and implications for survival in patients with squamous cell carcinoma of the tongue

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