Open AccessTumor‐infiltrating M2 macrophage in pretreatment biopsy sample predicts response to chemotherapy and survival in esophageal cancer
Author(s) -
Yamamoto Kei,
Makino Tomoki,
Sato Eiichi,
Noma Toshiki,
Urakawa Shinya,
Takeoka Tomohira,
Yamashita Kotaro,
Saito Takuro,
Tanaka Koji,
Takahashi Tsuyoshi,
Kurokawa Yukinori,
Yamasaki Makoto,
Nakajima Kiyokazu,
Mori Masaki,
Doki Yuichiro,
Wada Hisashi
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14328
Subject(s) - cd163 , cd68 , tumor associated macrophage , tumor microenvironment , foxp3 , infiltration (hvac) , medicine , immunohistochemistry , tumor infiltrating lymphocytes , biopsy , immune system , chemotherapy , pathological , pathology , cd8 , macrophage , oncology , immunology , biology , biochemistry , physics , in vitro , thermodynamics
The association between the tumor microenvironment (TME) and treatment response or survival has been a recent focus in several types of cancer. However, most study materials are resected specimens that were completely modified by prior chemotherapy; therefore, the unmodified host immune condition has not yet been clarified. The aim of the present study was to evaluate the relationship between TME assessed in pre–therapeutic biopsy samples and chemoresistance in esophageal cancer (EC). A total of 86 endoscopic biopsy samples from EC patients who received neoadjuvant chemotherapy (NAC) prior to surgery were evaluated for the number of intratumoral CD4 + lymphocytes (with/without Foxp3 expression), CD8 + lymphocytes (with/without PD‐1 expression), monocytes (CD14 + ) and macrophages (CD86 + , CD163 + and CD206 + ) by multiplex immunohistochemistry (IHC). The number of tumor‐infiltrating CD206 + macrophages I significantly correlated with cT, cM, cStage and neutrophil/lymphocyte ratio (NLR), whereas the number of lymphocytes (including expression of Foxp3 and PD‐1) was not associated with clinico‐pathological features. The high infiltration of CD163 + or CD206 + macrophages was significantly associated with poor pathological response to NAC ( P = 0.0057 and 0.0196, respectively). Expression of arginase‐1 in CD163 + macrophages tended to be higher in non–responders (29.4% vs 18.2%, P = 0.17). In addition, patients with high infiltration of M2 macrophages exhibited unfavorable overall survival compared to those without high infiltration of M2 macrophages (5‐year overall survival 57.2% vs 71.0%, P = 0.0498). Thus, a comprehensive analysis of TME using multiplex IHC revealed that M2 macrophage infiltration would be useful in predicting the response to NAC and long‐term survival in EC patients.