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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.

Tumor‐associated CD 204 + M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma