Macrophage type 2 differentiation in a patient with laryngeal squamous cell carcinoma and metastatic prostate adenocarcinoma to the cervical lymph nodes

Abstract

BackgroundThe tumor microenvironment often polarizes infiltrating macrophages towards a type 2, or M2 phenotype, that is characterized by expression of various cysteine-rich, scavenger receptors, including CD163. The primary function of M2 macrophages is to facilitate wound healing. As such, they are capable of providing metabolic support to a growing tumor, neovascularization, as well as protection from cytotoxic T cells. The tumor microenvironment contains a milieu of secreted factors and vesicles, which in certain circumstances can gain access to lymphatic vessels that drain to local lymph nodes.Case presentationWe report a 59-year-old male with recurrent T4 squamous cell carcinoma (SCC) of the larynx with synchronous prostate adenocarcinoma confined to the prostate and regional pelvic lymph nodes, without metastatic disease. The patient underwent salvage total laryngectomy and bilateral neck dissection with final pathology revealing a recurrent moderately differentiated SCC involving the larynx as well as prostate cancer in draining level 4 cervical lymph nodes bilaterally. CD163 staining was performed on the primary tumor, a negative draining lymph node, and a level four lymph node with a focus of metastatic prostate cancer and compared to benign controls. The negative draining lymph node demonstrated a large CD163 population of cells as did the interface of the focus of prostate cancer and surrounding lymph node. CD163 levels were markedly increased in this patient compared to benign lymph node controls. The macrophage differentiation at the primary tumor in the larynx was strongly CD163 positive supporting an immune permissive environment for tumor growth and metastasis.ConclusionWe describe a unique case of solitary metastatic prostate cancer to cervical lymph nodes in the setting of a laryngeal cancer. These observations suggest that SCC-derived factors drive a tumor-supportive environment in draining lymph nodes dominated by an overwhelming number of CD163+, M2 macrophages. Lymph nodes that are ‘primed’ by SCC differentiation to M2 phenotype may be at higher risk of harboring metastases.

Tumor-associated macrophages and PD-L1 in prostate cancer: a possible key to unlocking immunotherapy efficacy

“…This was similar to a previous report by Marina Kazantseva and colleagues, which found that high levels of CD163+ TAM infiltration were associated with higher Gleason score [29]. Consistently, in cervical cancer and oral carcinomas, high levels of CD163+ TAMs infiltration were also associated with worse disease-free survival (DFS) [10,30,31]. Accumulated evidence suggests that a higher CD163+ TAMs count indicates poor prognosis and high metastatic potential in various cancers [32]; however, how CD163 works in the protumoral activation of TAMs remains unclear.…”

“…The functional polarization of TAMs and their spatial distribution have been shown to impact cancer aggressiveness, metastatic potential, and clinical outcomes for cancer patients [6][7][8]. TAMs play a crucial role in the intrinsic immune response, and different TAM subtypes possess distinct biological functions [9,10]. Histologically, TAMs are divided into classically activated M1-TAMs and alternatively activated M2-TAMs, characterized by their anti-tumor and pro-tumor properties, respectively [11].…”

Multi-lectin Affinity Chromatography and Quantitative Proteomic Analysis Reveal Differential Glycoform Levels between Prostate Cancer and Benign Prostatic Hyperplasia Sera

“…CD163 has also been associated with prostate cancer. Interestingly, CD163 (hemoglobin scavenger receptor M130), is a secreted glycoprotein expressed by tumor-associated type M2 macrophages, and has been reported to be associated with prostatic inflammation and upregulated in prostate cancer with regard to tumor extension, metastasis, and biochemical recurrence 57 – 60 . In this study, CD163 was only detected and quantitated in the AAL and PHA fractions (no non- or otherwise glycosylated forms), suggesting the presence of core-fucosylation and extensive branching of complex type glycans.…”

Macrophage/microglia polarization for the treatment of diabetic retinopathy

“…However, precisely because of the secretion of these factors and their overactivation, aberrant hyperplasia may result, such as pathological angiogenesis. Four distinct populations of M2 macrophages may be identified based on the multiple activation signals they receive: M2a, M2b, M2c, and M2d, whose surface markers include CD206, CD209, CD301, and CD163 ( 40 , 44 ). Type II cytokines, IL-4 or IL-13, activate M2a macrophages, which then secrete several pro-inflammatory cytokines, including IL-10 and arginase 1, and receptors, such as mannose receptor CD206 and macrophage galactose type C lectin (MGL; CD301) ( 40 ).…”