title: CD14+macrophage-like cells as the linchpin of cervical cancer perpetrated immune suppression and early metastatic spread: A new therapeutic lead?
abstract: A number of studies point to an aberrant differentiation and accumulation of CD14+PD-L1+M2-macrophage-like cells in the microenvironment of cervical cancer, which promote immunosuppressive conditions and are associated with tumor invasion, angiogenesis and metastasis. Therapeutic targeting of these macrophages may tip the balance in favor of antitumor immunity. Cervical cancer is the fourth most common cancer among women worldwide and is caused by a persistent infection and subsequent integration of high-risk types of the human papillomavirus. Continuous expression of the viral oncoproteins E6 and E7 has been shown essential to maintain the transformed state of infected keratinocytes. As these non-self oncoproteins are immunogenic, cervical cancer requires a highly immune suppressed tumor microenvironment to metastasize through lymphovascular space invasion (LVSI) to the pelvic tumor-draining lymph nodes (TDLN). Unraveling the mechanisms underlying this immune suppression may uncover novel therapeutic targets aimed at loco-regional control of cervical cancer.
authors.affiliation: Department of Medical Oncology; VU University Medical Center-Cancer Center Amsterdam ; De Boelelaan, Amsterdam, The Netherlands ; Center Gynecological Oncology Amsterdam (CGOA); Department of Obstetrics and Gynecology; VU University Medical Center ; De Boelelaan, Amsterdam, The Netherlands.
authors.forename: A Marijne
authors.initials: AM
authors.lastname: Heeren
authors.affiliation: Center Gynecological Oncology Amsterdam (CGOA); Department of Obstetrics and Gynecology; VU University Medical Center ; De Boelelaan, Amsterdam, The Netherlands ; Center Gynecological Oncology Amsterdam (CGOA); Department of Gynecology; Netherlands Cancer Institute - Antoni van Leeuwenhoek ; Amsterdam, The Netherlands ; Center Gynecological Oncology Amsterdam (CGOA); Department of Obstetrics and Gynecology; Academic Medical Center ; Amsterdam, The Netherlands.
authors.forename: Gemma G
authors.initials: GG
authors.lastname: Kenter
authors.affiliation: Center Gynecological Oncology Amsterdam (CGOA); Department of Obstetrics and Gynecology; VU University Medical Center ; De Boelelaan, Amsterdam, The Netherlands.
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Jordanova
authors.affiliation: Department of Medical Oncology; VU University Medical Center-Cancer Center Amsterdam ; De Boelelaan, Amsterdam, The Netherlands.
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
keywords: COX, cyclooxygenase; DC, dendritic cell; IL, interleukin; LVSI, lymphovascular space invasion; MDSC, myeloid-derived suppressor cells; PD-L1; PD-L1, programmed death-ligand 1; PGE2, prostaglandin-E2; TDLN, tumor-draining lymph node; Treg, regulatory T cell; cervical cancer; dendritic cells; immunotherapy; macrophages; tumor microenvironment; tumor-draining lymph nodes