Tumor‐associated CD204⁺ M2 macrophages are unfavorable prognostic indicators in uterine cervical adenocarcinoma

Abstract

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 CD204+ M2 macrophages was significantly associated with shorter disease‐free survival, although no other tumor‐infiltrating immune cells were prognostic, including CD4+, CD8+, FOXP3+, and PD‐1+ lymphocytes and CD68+ 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 CD204+ M2 macrophages may predict poor prognoses in patients with cervical adenocarcinoma.

CD20+ tumor‐infiltrating immune cells and CD204+ M2 macrophages are associated with prognosis in thymic carcinoma

“…To our knowledge, this study is the first report demonstrating the prognostic effect of the ratios of CD8 + /CD204 + and CD20 + /CD204 + tumor‐infiltrating cells and their significant association with the overall DFS. The significance of the ratio of CD8 + /CD204 + TIIC has also been reported in esophageal carcinoma and uterine cervical adenocarcinoma 48,49 . Compared to the single immune cells, their ratios were found to be consistent among regions (tumor islets and stroma) and values (maximum, mean and median) in this study.…”

Integrative analysis of gene expression and DNA methylation through one‐class logistic regression machine learning identifies stemness features in medulloblastoma

“…These two results contradict the common view of tumor-promoting M2 macrophages and tumor-suppressing M1 macrophages. In many cancer types, M2 macrophage counts are associated with adverse outcomes Jensen et al, 2009;Kawachi et al, 2018;Medrek et al, 2012), and M1 macrophage infiltration is correlated with better prognosis (Ma et al, 2010;Mei et al, 2016). However, several studies suggest that the dichotomous M1/M2 classification of macrophages is oversimplified, and the role of tumor-associated macrophages is still controversial (Martinez and Gordon, 2014;Van Overmeire et al, 2014).…”

CD3+CD56+ natural killer T cell infiltration is increased in cervical cancer and negatively correlated with tumour progression

“…It is discovered that a large number of monocyte lymphocytes infiltrate cervical cancer tissues, but they are still unable to prevent the metastasis of cancer cells, indicating that cancer cells have the ability to escape immunological surveillance [28]. CD3 þ CD56 þ NKT cells are a kind of natural immune cells with strong heterogeneity [29]. They directly recognize and kill tumour cells, play a role of immune regulation by secreting Th1 or Th2 cytokines and have potential clinical application value in cancer treatment [29].…”