The tumor microenvironment at a glance

Balkwill, Frances R.; Capasso, Melania; Hagemann, Thorsten

doi:10.1242/jcs.116392

Cited by 1,468 publications

(1,185 citation statements)

References 94 publications

(95 reference statements)

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“…Moreover, the very same type of cell can be influenced by the microenvironment to polarize into different functional states according to the need for an active immune response or of immune tolerance at a certain moment. This has been demonstrated for macrophages (M1 and M2 polarization), [8][9][10][11] neutrophils (N1 and N2 polarization) 12,13 and T lymphocytes (Th1, Th2, Th17 responses). [14][15][16] The role of T lymphocytes and macrophages has been extensively studied in melanoma, 13,[17][18][19][20][21][22] whereas less is known on the role of B lymphocytes and plasma cells (PCs).…”

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confidence: 70%

Plasma cells in primary melanoma. Prognostic significance and possible role of IgA

et al. 2016

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Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma cells (PCs), in particular, are still obscure. The aim of this study was to characterize pathological features and clinical outcome of primary cutaneous melanomas associated with PCs. Moreover, we investigated the origins of the melanoma-associated PCs. Finally, we studied the outcome of patients with primary melanomas with PCs. We reviewed 710 melanomas to correlate the presence of PCs with histological prognostic markers. Immunohistochemistry for CD138 and heavy and light chains was performed in primary melanomas (PM) and in loco-regional lymph nodes (LN), both metastatic and not metastatic. In three PM and nine LN with frozen material, VDJ-rearrangement was analyzed by Gene Scan Analysis. Survival analysis was performed on a group of 85 primary melanomas 42 mm in thickness. Forty-one cases (3.7%) showed clusters/sheets of PCs. PC-rich melanomas occurred at an older age and were thicker, more often ulcerated and more mitotically active (Po 0.05). PCs were polyclonal and often expressed IgA in addition to IgG. In LN, clusters/sheets of IgA+ PCs were found both in the sinuses and subcapsular areas. Analysis of VDJ-rearrangements showed the IgA to be oligoclonal. Melanomas with clusters/sheets of PCs had a significantly worse survival compared with melanomas without PCs while, interestingly, melanomas with sparse PCs were associated with a better clinical outcome (P = 0.002). In conclusion, melanomas with sheets/clusters of PCs are associated with worse prognosis. IgG and IgA are the isotypes predominantly produced by these PCs. IgA oligoclonality suggests an antigen-driven response that facilitates melanoma progression by a hitherto unknown mechanism.

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confidence: 70%

Plasma cells in primary melanoma. Prognostic significance and possible role of IgA

et al. 2016

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“…MDSCs and Treg cells have been known as two major immunosuppressive cell types in tumor microenvironment that suppress antitumor T cell immunity. 23 In addition, macrophages in tumor microenvironment can be reset to become tumor-associated macrophages (TAM) that are also conferred with an immunosuppressive function. 24 Notably, MDSCs, Treg cells and TAMs may interact with each other and form an immunosuppressive triangle in tumor microenvironment.…”

Section: Macrophages Remodel Tumor Microenvironment After the Combinementioning

confidence: 99%

Chemotherapeutic tumor microparticles combining low-dose irradiation reprogram tumor-promoting macrophages through a tumor-repopulating cell-curtailing pathway

et al. 2017

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Stem cell-like tumor-repopulating cells (TRCs) have a critical role in establishing a tumor immunosuppressive microenvironment. However, means to enhance antitumor immunity by disrupting TRCs are absent. Our previous studies have shown that tumor cell-derived microparticles (T-MPs) preferentially abrogate TRCs by delivering antitumor drugs into nuclei of TRCs. Here, we show that low dose irradiation (LDI) enhances the effect of cisplatin-packaging T-MPs (Cis-MPs) on TRCs, leading to inhibiting tumor growth in different tumor models. This antitumor effect is not due to the direct killing of tumor cells but is T cell-dependent and relies on macrophages for their efficacy. The underlying mechanism is involved in therapeutic reprograming macrophages from tumor-promotion to tumorinhibition by disrupting TRCs and curtailing their vicious education on macrophages. These findings provide a novel strategy to reset macrophage polarization and confer their function more like M1 than M2 types with highly promising potential clinical applications.

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“…17 The important role that inflammation plays in cancer and operative outcomes is being increasingly recognized. [18][19][20][21][22] Increased preoperative NLR may be an important indicator of the inflammatory state of patient at the time of surgery. This marker is easily obtained from a patient's routine preoperative laboratory studies and is easily calculated.…”

Section: Introductionmentioning

confidence: 99%

Elevated NLR in gallbladder cancer and cholangiocarcinoma – making bad cancers even worse: results from the US Extrahepatic Biliary Malignancy Consortium

Beal

Wei

Ethun

et al. 2016

HPB

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The tumor microenvironment at a glance

Cited by 1,468 publications

References 94 publications

Plasma cells in primary melanoma. Prognostic significance and possible role of IgA

Plasma cells in primary melanoma. Prognostic significance and possible role of IgA

Chemotherapeutic tumor microparticles combining low-dose irradiation reprogram tumor-promoting macrophages through a tumor-repopulating cell-curtailing pathway

Elevated NLR in gallbladder cancer and cholangiocarcinoma – making bad cancers even worse: results from the US Extrahepatic Biliary Malignancy Consortium

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