Robust response to nivolumab in patient with renal cell carcinoma inferior vena cava tumour thrombus

Berends, Joel; Gourley, Eric; Kaushik, Dharam

doi:10.1136/bcr-2018-227030

Cited by 10 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 1 Additionally, a case report of a 47-year-old male with mRCC and IVC tumour thrombus who at baseline had no evidence of PE or deep venous thrombosis and had an IVC filter insitu was started on nivolumab. One year after initiation of treatment but 4 months following investigations demonstrating absence of TEs, he developed a diffuse distribution of thromboses in superior and inferior mesenteric veins, splenic vein and portal vein 5 that parallels a significant hypercoagulable state post IO therapy which occurs in our case.…”

Section: Discussionsupporting

confidence: 59%

Immuno-oncology therapy associated thromboembolic events in metastatic renal cell carcinoma

Alhamdani

Alberto

Ischia

2023

Urology Case Reports

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 59%

Immuno-oncology therapy associated thromboembolic events in metastatic renal cell carcinoma

Alhamdani

Alberto

Ischia

2023

Urology Case Reports

View full text Add to dashboard Cite

“…Considering that recent studies have observed dramatic reduction of tumor thrombus in ccRCC patients after ICB therapy [ 23 – 26 ], we speculated that tumor-infiltrating immune cells may play important roles in the process. Therefore, we first performed unsupervised clustering of T and NK cells and obtained 12 clusters across ARTs, PTs and TTs, including four subtypes of CD4 + T cells (CD4-C1 to CD4-C4), five subclusters of CD8 + T cells (CD8-C1 to CD8-C5), two NK subclusters (NK1 and NK2) and one NKT cluster (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…There are evidences showed that certain CD8 + T cells in the progenitor exhausted state could enhance the efficacy of immune checkpoint blockade (ICB) therapy in melanoma and kidney cancer [ 37 , 38 ]. Meanwhile, considering a striking regression of TTs with ICB therapy in some ccRCC patients [ 23 – 26 ], we asked whether there was certain subset of CD8 + T cells we recovered may resemble the progenitor exhausted phenotype. Then, we scored the CD8 + T cell subclusters for progenitor and terminally exhausted gene signatures according to the published studies [ 37 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

“…However, the percentage of benefited patients showing thrombus regression from these treatments were extremely variable (from 25 to 67%) in different clinical studies [ 12 ]. Specifically, neoadjuvant immunotherapy was only effectively reducing the tumor thrombus size in some patients [ 23 – 26 ]. Thus, systematically deciphering the molecular differences between tumor thrombus and primary tumors is urgently needed for the development of new predictive markers and more effective therapies for ccRCC with TTs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Decoding the multicellular ecosystem of vena caval tumor thrombus in clear cell renal cell carcinoma by single-cell RNA sequencing

Shi

Zhang

et al. 2022

Genome Biol

View full text Add to dashboard Cite

Background Vascular invasion with tumor thrombus frequently occurs in advanced renal cell carcinoma (RCC). Thrombectomy is one of the most challenging surgeries with high rate of perioperative morbidity and mortality. However, the mechanisms driving tumor thrombus formation are poorly understood which is required for designing effective therapy for eliminating tumor thrombus. Results We perform single-cell RNA sequencing analysis of 19 surgical tissue specimens from 8 clear cell renal cell carcinoma (ccRCC) patients with tumor thrombus. We observe tumor thrombus has increased tissue resident CD8+ T cells with a progenitor exhausted phenotype compared with the matched primary tumors. Remarkably, macrophages, malignant cells, endothelial cells and myofibroblasts from TTs exhibit enhanced remodeling of the extracellular matrix. The macrophages and malignant cells from primary tumors represent proinflammatory states, but also increase the expression of immunosuppressive markers compared to tumor thrombus. Finally, differential gene expression and interaction analyses reveal that tumor-stroma interplay reshapes the extracellular matrix in tumor thrombus associated with poor survival. Conclusions Our comprehensive picture of the ecosystem of ccRCC with tumor thrombus provides deeper insights into the mechanisms of tumor thrombus formation, which may aid in the design of effective neoadjuvant therapy to promote downstaging of tumor thrombus and decrease the perioperative morbidity and mortality of thrombectomy.

show abstract

“…Downstaging of the VTT through neoadjuvant treatment with ICIs can play an important role in minimizing surgical complications. The positive impact of the use of ICIs as neoadjuvant therapies in aRCC and mRCC cases with VTT has been reported [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

Comparison of PD-L1 Scores in Primary Kidney Tumors Versus Accompanying Venous Tumor Thrombi: Retrospective, Comparative, Monocentric Study in Treatment-Naive Patients

et al. 2021

View full text Add to dashboard Cite

Introduction Renal cell carcinoma (RCC), an immunogenic tumor, is the most common form of kidney cancer worldwide. Immune checkpoint inhibitors (ICIs) play an important role in the treatment of metastatic RCC. Programmed death-ligand (PD-L1) has already been proposed as a possible prognosticator for ICIs effectiveness. To elucidate the feasible role of ICIs in neoadjuvant settings, we have assessed the most common PD-L1 expression modalities [tumor proportion score (TPS), combined positivity score (CPS) and inflammatory cell (IC) score] in primary tumors (PTs) and venous tumor thrombi (VTT) in first diagnosed, previously untreated RCC patients with accompanying VTT. Methods Between January 1999 and December 2016, 71 patients with a first diagnosed, untreated, locally advanced RCC (aRCC) (≥ pT3a) underwent surgery in Hanover Medical School (MHH). PD-L1 expression was examined separately in PTs and VTT using the CPS, IC score and TPS. We also considered the age at the time of the initial surgery and gender as probable influencing factors. By using a cutoff value of 1 (1%), PD-L1 expression levels in PTs and VTT were assessed to enable the determination of any frequency differences. Results Positive scores for PTs were shown by 54 (CPS), 53 (IC score) and 34 (TPS) patients, whereas in VTT, positive scores were evaluated for a total of 50 (CPS), 47 (IC-score) and 36 (TPS) patients. No statistically significant differences were obtained between the PD-L1 expression immunoscores for PTs and VTT. The covariates age at the time of the initial surgery and gender could not be statistically proven to influence the differences in PD-L1 expression between the VTT and PTs. Conclusion To the best of our knowledge, this research is the largest study to investigate PD-L1 expression in PTs and VTT in 71 cases. It could have relevance for the future development of neoadjuvant immunotherapy options, particularly in aRCC with VTT.

show abstract

Robust response to nivolumab in patient with renal cell carcinoma inferior vena cava tumour thrombus

Cited by 10 publications

References 23 publications

Immuno-oncology therapy associated thromboembolic events in metastatic renal cell carcinoma

Immuno-oncology therapy associated thromboembolic events in metastatic renal cell carcinoma

Decoding the multicellular ecosystem of vena caval tumor thrombus in clear cell renal cell carcinoma by single-cell RNA sequencing

Comparison of PD-L1 Scores in Primary Kidney Tumors Versus Accompanying Venous Tumor Thrombi: Retrospective, Comparative, Monocentric Study in Treatment-Naive Patients

Contact Info

Product

Resources

About