CSF1R Protein Expression in Reactive Lymphoid Tissues and Lymphoma: Its Relevance in Classical Hodgkin Lymphoma

Martín‐Moreno, Ana M.; Roncador, Giovanna; Maestre, Lorena; Mata, Elena; Jiménez, Scherezade; Martı́nez-Torrecuadrada, Jorge L.; Reyes-García, Ana Isabel; Rubio, Carmen; Tomás, José Francisco; Estévez, Mónica; Pulford, Karen; Piris, Miguel Á.; Garcı́a, Juan F.

doi:10.1371/journal.pone.0125203

Cited by 31 publications

(42 citation statements)

References 43 publications

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“…The THE1B-CSF1R transcript produces a full-length protein in HL, which is required for growth/survival of HL cell lines [113] and is clinically prognostic for poorer patient survival [115]. Ectopic CSF1R expression in HL appears to be completely dependent on the THE1B LTR, and CSF1R protein or mRNA is detected in 39–48% of HL patient samples [115, 116]. …”

Section: Introductionmentioning

confidence: 99%

Endogenous retroviral promoter exaptation in human cancer

2016

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Cancer arises from a series of genetic and epigenetic changes, which result in abnormal expression or mutational activation of oncogenes, as well as suppression/inactivation of tumor suppressor genes. Aberrant expression of coding genes or long non-coding RNAs (lncRNAs) with oncogenic properties can be caused by translocations, gene amplifications, point mutations or other less characterized mechanisms. One such mechanism is the inappropriate usage of normally dormant, tissue-restricted or cryptic enhancers or promoters that serve to drive oncogenic gene expression. Dispersed across the human genome, endogenous retroviruses (ERVs) provide an enormous reservoir of autonomous gene regulatory modules, some of which have been co-opted by the host during evolution to play important roles in normal regulation of genes and gene networks. This review focuses on the “dark side” of such ERV regulatory capacity. Specifically, we discuss a growing number of examples of normally dormant or epigenetically repressed ERVs that have been harnessed to drive oncogenes in human cancer, a process we term onco-exaptation, and we propose potential mechanisms that may underlie this phenomenon.

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Section: Introductionmentioning

confidence: 99%

Endogenous retroviral promoter exaptation in human cancer

2016

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“…Using immunohistochemical costaining, we examined the samples for CSF-1R, CD68, CD163, CD16, and slan expression. The anti-CSF-1R used in this study has been validated on formalin-fixed archival tissue 21 as recognizing CD68 + M s in reactive lymph nodes, as well as TAMs in human lymphomas. 21 As expected, primary carcinomas are largely devoid of slan + cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The anti-CSF-1R used in this study has been validated on formalin-fixed archival tissue 21 as recognizing CD68 + M s in reactive lymph nodes, as well as TAMs in human lymphomas. 21 As expected, primary carcinomas are largely devoid of slan + cells ( Fig. 1B and G), whereas numerous CSF-1R + cells are detectable in the tumor microenvironment ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Potential contribution of tumor-associated slan+ cells as anti-CSF-1R targets in human carcinoma

Lonardi

Licini

Micheletti

et al. 2017

Journal of Leukocyte Biology

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The precise identification of the types and respective roles of the tumor-associated myeloid cells, which include tumor-associated Mϕs (TAMs), neutrophils, dendritic cells, and myeloid-derived suppressor cells, is under intensive investigation. Although tumor-associated myeloid cells may contribute to tumor cell eradication by virtue of their effector functions, they are retained to fulfill predominantly protumorigenic roles. It follows that depletion of tumor-associated myeloid cells represents one of the currently pursued therapeutic options in advanced malignancies. In that regard, RG7155/emactuzumab, a specific anti-CSF-1R humanized Ab, has been reported recently to deplete CSF-1R TAMs, in association with objective clinical responses in patients with advanced cancer. Because RG7155/emactuzumab has also been shown to deplete blood non-classic CD14 CD16 monocytes, which in large part include the CD16 slan monocytes, we asked whether RG7155/emactuzumab could target tumor-associated slan cells. In this study, we confirmed that slan cells localize only to metastatic tumor-draining lymph nodes, not to primary tumors or distant metastases in patients with different types of carcinoma. Notably, by cell scoring on serial sections, we found that slan cells represent a minor fraction of the total CSF-1R cell pool, suggesting that slan cells potentially represent minor targets of anti-CSF-1R therapy. Therefore, a protumorigenic role for slan cells, such as that of CSF-1R TAMs, based on our current data, remains questionable.

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“…Higher numbers of CD68 + macrophages within tumor tissues were associated with shorter progression‐free survival . CD163 and CSF1R expression have also been linked to survival . Emerging data also highlights the potential relationship between the number of regulatory T‐cells and outcome in adults .…”

Section: Introductionmentioning

confidence: 98%

“…Recent studies have linked tumor associated macrophages with outcome . Higher numbers of CD68 + macrophages within tumor tissues were associated with shorter progression‐free survival .…”

Section: Introductionmentioning

confidence: 99%