Gene Expression Profiling in Kidney Transplant Recipients on Immune Checkpoint Inhibitors

2021 ◽  
Vol 16 (9) ◽  
pp. 1315-1317
Author(s):  
Priyanka Jethwani ◽  
Anushree C. Shirali
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Kidney Transplant ◽  
Immune Checkpoint ◽  
Expression Profiling ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

scholarly journals Immune-checkpoint inhibitors in renal transplanted patients affected by melanoma: a systematic review

Immunotherapy ◽  
2021 ◽  
Author(s):  
Ernesto Rossi ◽  
Giovanni Schinzari ◽  
Brigida Anna Maiorano ◽  
Ilaria Esposito ◽  
Anna Acampora ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Complete Response ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Appropriate Treatment ◽  
Increased Risk ◽  
Risk Of Cancer

Kidney transplantation leads to an increased risk of cancer. Melanoma is one of the most frequent neoplasms in kidney transplant recipients. Transplanted patients were excluded from trials with checkpoint inhibitors in melanoma. The authors performed a systematic review regarding the use of anti-PD1 and anti-CTLA4 agents in renal transplanted patients with melanoma. Thirty-four cases were included (24 progressive disease, eight partial responses and one stable disease) but no complete response were reported. Fourteen graft rejections were observed, especially with anti-PD1 agent. The median time from the start of immune-checkpoint inhibitor and rejection was 21 days. Response rate was similar between patients with rejection and patients without rejection. The benefit of immune-checkpoint inhibitors versus the risk of allograft rejection should be carefully weighted for each patient. A multidisciplinary approach should be considered to discuss the most appropriate treatment for every case, given the aggressiveness of melanoma in these subsets of patients.

scholarly journals The Efficacy of Anti-PD-L1 Treatment in Melanoma Is Associated with the Expression of the ECM Molecule EMILIN2

2021 ◽  
Vol 22 (14) ◽  
pp. 7511
Author(s):  
Albina Fejza ◽  
Maurizio Polano ◽  
Lucrezia Camicia ◽  
Evelina Poletto ◽  
Greta Carobolante ◽  
...  
Keyword(s):  
Gene Expression ◽  
Effective Treatment ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tumor Hypoxia ◽  
Melanoma Cells ◽  
Vessel Normalization ◽  
Melanoma Patients

The use of immune checkpoint inhibitors has revolutionized the treatment of melanoma patients, leading to remarkable improvements in the cure. However, to ensure a safe and effective treatment, there is the need to develop markers to identify the patients that would most likely respond to the therapies. The microenvironment is gaining attention in this context, since it can regulate both the immunotherapy efficacyand angiogenesis, which is known to be affected by treatment. Here, we investigated the putative role of the ECM molecule EMILIN-2, a tumor suppressive and pro-angiogenic molecule. We verified that the EMILIN2 expression is variable among melanoma patients and is associated with the response to PD-L1 inhibitors. Consistently, in preclinical settings,the absence of EMILIN-2 is associated with higher PD-L1 expression and increased immunotherapy efficacy. We verified that EMILIN-2 modulates PD-L1 expression in melanoma cells through indirect immune-dependent mechanisms. Notably, upon PD-L1 blockage, Emilin2−/− mice displayed improved intra-tumoral vessel normalization and decreased tumor hypoxia. Finally, we provide evidence indicating that the inclusion of EMILIN2 in a number of gene expression signatures improves their predictive potential, a further indication that the analysis of this molecule may be key for the development of new markers to predict immunotherapy efficacy.

Immune Checkpoint Inhibitors in Thoracic Transplant Recipients: A Registry Initiative

2020 ◽  
Vol 39 (4) ◽  
pp. S210
Author(s):  
A. Daud ◽  
M.R. Mehra ◽  
A. Siu ◽  
M.R. Johnson ◽  
M. Perch ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Transplant Recipients

Association of immune gene expression profiling with vinflunine clinical benefit in metastatic urothelial cancer (mUC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16034-e16034
Author(s):  
Guillermo de Velasco ◽  
Marta Dueñas ◽  
Alejandra Bernardini ◽  
Alvaro Pinto ◽  
Teresa Alonso-Gordoa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Clinical Benefit ◽  
Expression Profiling ◽  
Checkpoint Inhibitors ◽  
Gene Profiling ◽  
Immune Gene ◽  
Similar Frequency ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

e16034 Background: There are limited treatment options for mUC after platinum-based chemotherapy failure. Immune checkpoint inhibitors (ICI) have shown a durable benefit but only in a minority of patients (20-25%). Vinflunine remains as a therapeutic option without validated biomarkers. In this study, we sought to analyze the molecular determinants of vinflunine response in mUC. Methods: mUC patients from 4 University Hospitals in Spain who received second-line vinflunine after platinum-based chemotherapy were classified in non-responders (NR: progressive disease ≤3 months; N = 10) or responders (R: response ≥ 6 months, N = 14). Targeted- sequencing of 275 cancer-related genes and a PanCancer Immune Profiling Panel were performed on pre-treatment tumors. Selected genes were evaluated by RT-qPCR and protein expression was detected by immunohistochemistry. Results: The most common alteration, TP53 mutations, had a similar frequency in R (7/14, 50%) and NR (4/10, 40%). Mutations in 5 genes: ERBB3 (4/14; 28,6%), KTM2C (4/14; 28,6%), PI3KCA (4/14; 28,6%), ARID2 (3/14; 21,4%) and FGFR3 (3/14; 21,4%) were identified only in R. Mutations in ERBB4 (3/10, 33,3%) and BCOR (2/10, 20%) were identified only in NR. Estimated TMBs were not significantly different among the R (13 per Mb) and NR (9 per Mb) samples. According to gene expression profiling, NR had high cytotoxic cells infiltrate and T cells as well as high counts of TILs compared to R. In addition, expression of IDO, MAGE A4, and SOCS1, that has been associated with response to ICIs, were down-regulated in R compared with NR. Conclusions: Gene profiling showed that low-expression levels of immune-related genes are significantly associated with clinical benefit from vinflunine. Validation and complementary studies are ongoing in patients treated with ICIs.

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