Immunotherapy in renal cell carcinoma: latest evidence and clinical implications

Santoni, Matteo; Massari, Francesco; Nunno, Vincenzo Di; Conti, Alessandro; Cimadamore, Alessia; Scarpelli, Marina; Montironi, Rodolfo; Cheng, Liang; Battelli, Nicola; López-Beltrán, Antonio

doi:10.7573/dic.212528

Cited by 74 publications

(48 citation statements)

References 49 publications

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“…Since then, and with the advent of immune-checkpoint inhibitors, several clinical trials have shown and are still addressing the effect of combining agents targeting PD-L1/PD-1 with anti-VEGFR tyrosine kinase inhibitors (TKI) [85]. The success indicated by these studies led to the recent approval of Nivolumab, which proved better in improving overall-survival and also was better tolerated when compared to everolimus in VEGF-refractory patients [86].…”

Section: Immune Therapies -Brief Overview In Kidney Cancermentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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In the last years, we have witnessed remarkable advances in targeted therapies for cancer patients. There is a growing effort to either replace or reduce the dose of unspecific, systemic (chemo)therapies, given the associated short- and long-term side effects, by introducing more specific targeted therapies as single or combination agents. Due to the well-known implications of the immune system and epigenetic landscape in modulating cancer development, both have been explored as potential targets in several malignancies, including those affecting the genitourinary tract. As the immune system function is also epigenetically regulated, there is rationale for combining both strategies. However, this is still rather underexplored, namely in urological tumors. We aim to briefly review the use of immune therapies in prostate, kidney, bladder, and testicular cancer, and further describe studies providing supporting evidence on their combination with epigenetic-based therapies.

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Section: Immune Therapies -Brief Overview In Kidney Cancermentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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“…ChRCC came to a similar conclusion [23]. Immunotherapy has also recently emerged as another option to treat metastatic RCC, and clinical trials that compare TKI therapy vs. immunotherapy are currently underway, although these studies have only enrolled patients with ccRCC [24]. e role of immunotherapy in treating nccRCC, for now, remains an open question.…”

Section: Case Reports In Urologymentioning

confidence: 93%

Exceptional Response of Metastatic Chromophobe Renal Cell Carcinoma to Vascular Endothelial Growth Factor (VEGF) Inhibitors: Should Increased VEGF-C Expression Be Used to Guide Treatment?

Bruinius

Dykema

Noyes

et al. 2019

Case Reports in Urology

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There is sparse literature demonstrating effective treatments for metastatic chromophobe renal cell carcinoma (ChRCC). The tyrosine kinase inhibitor (TKI) sunitinib selectively inhibits the VEGF pathway and it is a standard care for metastatic clear cell renal cell carcinoma (ccRCC), although data supporting its use in ChRCC is much more limited. A 56-year-old underwent palliative nephrectomy for locally-advanced ChRCC with sarcomatoid differentiation. Tumor gene expression profiling using Affymetrix HG-U133 Plus 2.0 GeneChip platform demonstrated significantly elevated VEGF-C expression compared to normal renal tissue n=12 and other types RCC n=158. Adjuvant sunitinib was used to treat his residual unresectable retroperitoneal lymph nodes. He demonstrated an exceptional response and underwent complete surgical resection four months later. He has been managed with TKIs for nearly nine years with only minimal disease progression. Additional studies exploring treatment options for patients with non-clear cell RCC are needed; in their absence, we would recommend TKIs for patients whose tumors bear a similar molecular profile.

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“…Similarly, expression of PD-1 by the TILs or expression of PD-L1 by the tumour cells are both associated with worse prognosis in ccRCC [22,23]. In turn, immunotherapy in forms of PD-1/PD-L1 inhibition appears to be useful in ccRCC management, and monoclonal antibodies targeting PD-1/PD-L1 may be combined with tyrosine kinase inhibitors (TKIs) and CTLA4 inhibitors [24,25].…”

Section: Introductionmentioning

confidence: 99%

Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored

et al. 2020

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Background: Clear cell renal cell carcinoma (ccRCC) is a markedly heterogeneous disease in many aspects, including the tumour microenvironment. Our previous study showed the importance of the tumour microenvironment in ccRCC xeno-transplant success rates. In order to better understand the potential relationship between TICs and the immune microenvironment, we employed a multi-modal approach, examining RNA and protein expression (flow cytometry, immunohistochemistry). Methods: We first examined the gene expression pattern of 18 stem/progenitor marker genes in the cancer genome atlas (TCGA) ccRCC cohort. Flow cytometry was next employed to examine lineage-specific expression levels of stem/progenitor markers and immune population makeup in six, disaggregated, primary ccRCC specimens. Immunohistochemistry was performed on a commercial ccRCC tissue microarray (TMA). Results: The 18 genes differed with respect to their correlation patterns with one another and to their prognostic significance. By flow cytometry, correlating expression frequency of 12 stem/progenitor markers and CD10 resulted in two clusters-one with CD10 (marker of proximal tubular differentiation), and second cluster containing mostly mesenchymal stem cell (MSC) markers, including CD146. In turn, these clusters differed with respect to their correlation with different CD45 + lineage markers and their expression of immune checkpoint pathway proteins. To confirm these findings, four stem/progenitor marker expression patterns were compared with CD4, CD8 and CD20 in a ccRCC TMA which showed a number of similar trends with respect to frequency of the different tumourinfiltrating leukocytes. Conclusion: Taken together, we observed heterogeneous but patterned expression levels of different stem/ progenitor markers. Our results suggest a non-random relationship between their expression patterns with the immune microenvironment populations in ccRCC.

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Immunotherapy in renal cell carcinoma: latest evidence and clinical implications

Cited by 74 publications

References 49 publications

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Exceptional Response of Metastatic Chromophobe Renal Cell Carcinoma to Vascular Endothelial Growth Factor (VEGF) Inhibitors: Should Increased VEGF-C Expression Be Used to Guide Treatment?

Stem/progenitor cell marker expression in clear cell renal cell carcinoma: a potential relationship with the immune microenvironment to be explored

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