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Cancers 2018, 10(8), 252; https://doi.org/10.3390/cancers10080252

CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining

1
Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan
2
Department of Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan
3
Bio Advanced Technology Division, Corporate R&D Headquarters, Konica Minolta, Inc., 1 Sakura-machi, Hino, Tokyo 191-8511, Japan
4
Department of Pathology, Saitama Cancer Center, 780 Komuro, Ina, Kitaadachi-gun, Saitama 362-0806, Japan
*
Author to whom correspondence should be addressed.
Received: 27 June 2018 / Revised: 16 July 2018 / Accepted: 27 July 2018 / Published: 31 July 2018
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Abstract

CSF1R-expressing tumor-associated macrophages (TAMs) induce a tumor-promoting microenvironment by regulating immunity. Evidence demonstrates that the expression and single nucleotide polymorphisms of CSF1R relate with survival and risk of lung cancer in never smokers. However, no previous studies have examined the association of CSF1R expression in TAMs with mortality or whether the prognostic association differs according to smoking status in lung adenocarcinoma. Quantitative phosphor-integrated dot staining was used to precisely assess CSF1R expression in TAMs. Using 195 consecutive cases of lung adenocarcinoma, we examined the association of CSF1R expression with mortality and whether the prognostic association differs according to smoking status. We observed high expression levels of CSF1R in TAMs in 65 of 195 (33%) cases of lung adenocarcinoma. High expression levels of CSF1R were associated with high lung cancer-specific mortality (log-rank p = 0.037; hazard ratio (HR) = 1.61, 95% confidence interval (CI) = 1.02−2.52, p = 0.043). This prognostic association differed according to smoking status (p for interaction = 0.049, between never-smoking and ever-smoking patients). The association between high expression levels of CSF1R and lung cancer-specific mortality was stronger in never-smoking patients (log-rank p = 0.0027; HR = 2.90, 95% CI = 1.41−6.11, p = 0.0041) than in ever-smoking patients (log-rank p = 0.73; HR = 1.11, 95% CI = 0.59−2.00, p = 0.73). The findings suggest that CSF1R-expressing TAMs may exert stronger tumor-promoting immunity in never-smoking patients with lung adenocarcinoma and serve as a therapeutic target in precision immunotherapies. View Full-Text
Keywords: CSF1R; tumor-associated macrophage (TAM); phosphor-integrated dot (PID); tobacco; non-small-cell lung cancer (NSCLC); immunohistochemistry; neoantigens; tumor mutational burden; immune checkpoint inhibitor; CD163 CSF1R; tumor-associated macrophage (TAM); phosphor-integrated dot (PID); tobacco; non-small-cell lung cancer (NSCLC); immunohistochemistry; neoantigens; tumor mutational burden; immune checkpoint inhibitor; CD163
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Inamura, K.; Shigematsu, Y.; Ninomiya, H.; Nakashima, Y.; Kobayashi, M.; Saito, H.; Takahashi, K.; Futaya, E.; Okumura, S.; Ishikawa, Y.; Kanda, H. CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining. Cancers 2018, 10, 252.

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