Immune signature of tumor infiltrating immune cells in renal cancer

Geißler, Katharina; Fornara, Paolo; Lautenschläger, Christine; Holzhausen, Hans-Jürgen; Seliger, Barbara; Riemann, Dagmar

doi:10.4161/2162402x.2014.985082

Cited by 146 publications

(137 citation statements)

References 36 publications

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“…Although we did not perform double staining for these markers, they were only expressed on macrophages and not on tumour cells and colocalized on serial immunostained sections. The presence of M2-TAM is associated with poor prognosis in a variety of tumour types including glioma, melanoma, carcinoma, some lymphomas and CCRCC [29][30][31][32][33]. We found high tumour infiltration by CD68 and CD163 expressing M2-TAM to be independently associated with shorter OS in the whole cohort and in the pT1 subgroup.…”

Section: Discussionmentioning

confidence: 69%

Nestin expression on tumour vessels and tumour-infiltrating macrophages define a poor prognosis subgroup of pt1 clear cell renal cell carcinoma

et al. 2016

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The behaviour of clear cell renal cell carcinoma (CCRCC) is highly unpredictable. Despite adequate initial surgery, 20 to 30 % of patients will develop local recurrence or metastasis during follow-up. Usual clinical and pathology parameters tend to classify most patients in an intermediate prognosis group, and molecular markers to determine prognosis more accurately are needed. A key feature of CCRCC is its abundant vascularization. Factors that upregulate angiogenesis, such as hypoxia and the presence of immune cells including macrophages, also modulate tumour proliferation and metastasis. We studied angiogenesis, as defined by nestin-positive capillaries, and tumour infiltration by macrophages especially in the good prognosis pT1 subgroup of CCRCC. We assessed whether these parameters are associated with metastatic extension and survival in CCRCC. The expression of HIF1α, CAIX, nestin, CD68 and CD163 was assessed by immunohistochemistry on a tissue microarray (TMA) containing tissue samples from 257 consecutive patients with sporadic CCRCC. Factors associated with progression-free (PFS) and overall survival (OS) were analysed. The presence of nestin-positive tumour vessels was independently associated with shorter PFS in the whole cohort and in the pT1 subgroup. The presence of tumour-infiltrating macrophages was independently associated with shorter OS in the whole cohort and in the pT1 subgroup. The presence of nestin-positive endothelial cells is associated with early relapse, especially in the pT1 subgroup and may help to select patients for antiangiogenic treatment. The presence of tumour-infiltrating M2-type macrophages is a strong predictor of short survival and may be used to adapt treatment strategy.

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Section: Discussionmentioning

confidence: 69%

Nestin expression on tumour vessels and tumour-infiltrating macrophages define a poor prognosis subgroup of pt1 clear cell renal cell carcinoma

et al. 2016

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“…Notably, among 19 cancer types examined by The Cancer Genome Atlas research programme, ccRCC has the highest T cell infiltration score 87 . Furthermore, higher nuclear grade and stage in ccRCC was correlated with an increase in T helper 2 and T regulatory cell infiltration 87,88 .…”

Section: Mechanisms/pathophysiologymentioning

confidence: 93%

Renal cell carcinoma

Hsieh

Purdue

Signoretti

et al. 2017

Nat Rev Dis Primers

1,804

1,599

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Renal cell carcinoma (RCC) denotes cancer originated from renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetics regulatory genes and demonstrated marked intratumour heterogeneity, which could have prognostic, predictive and therapeutic relevance. Localized RCC can be successfully managed with surgery whereas metastatic RCC is refractory to conventional chemotherapy. However, over the past decade, marked advances in treatment of metastatic RCC have been made, with targeted agents including sorafenib, sunitinib, bevacizumab, pazopanib and axitini that inhibit vascular endothelial growth factor (VEGF) and its receptor(VEGFR) and everolimus and temsirolimus, which inhibit mTOR complex 1, being approved. Since 2015, agents with additional targets aside from VEGFR have been approved, such as cabozantinib and lenvatinib; immunotherapies such as nivolumab have also been added to the armamentarium for metastatic RCC. Here, we provide an overview of the molecular biology of RCC, with a focus on ccRCC, as well as updates to complement current clinical guidelines and an outline of potential future directions for RCC research and therapy.

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“…Recent reports indicated that tumor-associated immune cells have been involved in the RCC initiation and progression, which could be an essential factor for the prediction of the outcome of tumor patients [5, 6]. Several immune cells in the RCC tumor microenvironment (TME), including macrophages, T cells, natural killer (NK) cells, dendritic cells (DCs) and neutrophils, might be recruited into RCC to exert their differential influences on tumor proliferation and invasion [7].…”

Section: Introductionmentioning

confidence: 99%

Infiltrating macrophages increase RCC epithelial mesenchymal transition (EMT) and stem cell-like populations via AKT and mTOR signaling

Zhao

Xie

et al. 2016

Oncotarget

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Infiltrating macrophages are a key component of inflammation during tumorigenesis and progression. However, the role of macrophages in renal cell carcinoma (RCC), especially in the stage of RCC malignant progression, is still unclear. Here, we found the macrophages could be recruited more easily into RCC tissues than the surrounding non-tumor tissues. In vitro co-culture system also confirmed RCC cells had a better capacity to recruit macrophages via CXCL8 signaling than normal renal epithelial cells. The consequences of recruiting more macrophages may then increase RCC cells invasion abilities. Mechanism dissection revealed that infiltrating macrophages could function through induction of epithelial-mesenchymal transition and increased cancer stem cell-like populations via activation of AKT/mTOR signal, and then led to increasing RCC cells invasion. The orthotopically xenografted mouse model with RCC cells and macrophages also confirmed that infiltrating macrophages could increase RCC cells progression via AKT/mTOR signal. Together, our results reveal a new mechanism that macrophages in the RCC tumor microenvironment could increase RCC metastasis via activation of the AKT/mTOR signals. Targeting this newly identified signaling may help us to better inhibit RCC metastasis.

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Immune signature of tumor infiltrating immune cells in renal cancer

Cited by 146 publications

References 36 publications

Nestin expression on tumour vessels and tumour-infiltrating macrophages define a poor prognosis subgroup of pt1 clear cell renal cell carcinoma

Nestin expression on tumour vessels and tumour-infiltrating macrophages define a poor prognosis subgroup of pt1 clear cell renal cell carcinoma

Renal cell carcinoma

Infiltrating macrophages increase RCC epithelial mesenchymal transition (EMT) and stem cell-like populations via AKT and mTOR signaling

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