Open AccessTumor‐associated CD 204 + M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma
Author(s) -
Kawachi Asuka,
Yoshida Hiroshi,
Kitano Shigehisa,
Ino Yoshinori,
Kato Tomoyasu,
Hiraoka Nobuyoshi
Publication year - 2018
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.13476
Subject(s) - stroma , adenocarcinoma , immunohistochemistry , immune system , medicine , tumor microenvironment , tumor infiltrating lymphocytes , pathology , cancer research , immunotherapy , immunology , cancer
Uterine cervical adenocarcinoma is rare, but its prevalence has increased. To improve outcomes and ensure the suitability of recent immunotherapies, the aim of this study was to evaluate the clinicopathological impact of the tumor immune microenvironment of uterine cervical adenocarcinoma. We investigated 148 adenocarcinoma cases, including 21 cases of adenocarcinoma in situ ( AIS ) and 127 cases of invasive adenocarcinoma, using immunohistochemistry to detect tumor‐infiltrating immune cells and the expression of programmed cell death 1 ligand‐1 ( PD ‐L1) and p16 on tumor cells. We then carried out correlation and survival analyses. The density of immune cells and expression levels were compared between the tumor cell nest and stroma and between AIS and invasive adenocarcinoma using digital image analysis. A higher density of tumor‐infiltrating CD 204 + M2 macrophages was significantly associated with shorter disease‐free survival, although no other tumor‐infiltrating immune cells were prognostic, including CD 4 + , CD 8 + , FOXP 3 + , and PD ‐1 + lymphocytes and CD 68 + macrophages. The density of stroma‐infiltrating lymphocytes and macrophages was significantly higher in invasive adenocarcinoma than in AIS . The density of tumor‐infiltrating lymphocytes in p16‐expressing human papillomavirus ( HPV )‐positive tumors was significantly higher than that in HPV ‐negative tumors. The HPV status was not associated with patient outcome. Expression of PD ‐L1 on tumor cells was found only in invasive adenocarcinoma cases (17.3%). A higher density of stroma‐infiltrating lymphocytes and macrophages was found in PD ‐L1‐positive tumors than in negative tumors. Patients with PD ‐L1‐positive tumors tended to experience longer survival. It is suggested that tumor‐infiltrating CD 204 + M2 macrophages may predict poor prognoses in patients with cervical adenocarcinoma.