Elucidating Durable Responses to Immune Checkpoint Inhibition

Rescigno, Pasquale; Aversa, Caterina; Seed, George; Lambros, Maryou; Gürel, Bora; Figueiredo, Ines; Bianchini, Diletta; Riisnaes, Ruth; Pereira, Rita; Maza, Maria D. Fenor de la; Carmichael, Juliet; Chandran, Khobe; Ferreira, Ana; Bertan, Claudia; Paschalis, Alec; Curcean, Andra; Sharp, Adam; Yuan, Wei; Tunariu, Nina; Poehlein, Christian; Carreira, Suzanne; Bono, Johann S. de

doi:10.1016/j.eururo.2020.06.056

Cited by 3 publications

(3 citation statements)

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“…Immunotherapy, including tumor vaccination and immune checkpoint inhibitors (ICIs), has become a treatment option for cancer with great promise. [38][39][40][41] For instance, sipuleucel-T is the first commercial autologous cell-based vaccination immunotherapy, which was found to be effective against metastatic castration-resistant prostate cancer (mCRPC). In addition, ICIs are under investigation for mCRPC, and it has shown efficacy in the treatment of a variety of diseases including PCa, and ICIs may have an effect on mCRPC patients.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, ICIs are under investigation for mCRPC, and it has shown efficacy in the treatment of a variety of diseases including PCa, and ICIs may have an effect on mCRPC patients. 39,40 Furthermore, mounting proofs have emphasized the essential regulatory effects of eRNA in the immune system and eRNA-targeted therapy in cancer, [42][43][44][45][46] which indicates that it has a promising prospect in the therapeutic choices of PCa. For example, oncogene-induced eRNAs can promote tumorigenesis under certain circumstances, such as KLK3e in PCa, an androgen receptor (AR)-induced eRNA.…”

Section: Discussionmentioning

confidence: 99%

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GAS1RR, an immune-related enhancer RNA, is related to biochemical recurrence-free survival in prostate cancer

Xiong

Xiao

et al. 2022

Exp Biol Med (Maywood)

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Prostate cancer (PCa) is one of the malignant tumors of urinary system with a high morbidity. Enhancer RNA is a subclass of long non-coding RNA transcribed from active enhancer regions, which plays a critical role in gene transcriptional regulation. However, the role of enhancer RNA (eRNA) in PCa remains extremely mysterious. This study is aimed at exploring key prognostic eRNAs in PCa. First, we downloaded gene expression data and clinical data of 33 cancer types from UCSC Xena platform. Second, we selected reported putative eRNA-target pairs and performed the Kaplan–Meier survival and correlation analysis to determine the crucial eRNAs most related to biochemical recurrence (BCR)-free survival. Third, we explored the clinical characteristics with the key eRNA GAS1 adjacent regulatory RNA (GAS1RR) and performed a computational difference algorithm and the Cox regression analysis. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the underlying mechanisms. Finally, we used the pan-cancer data from The Cancer Genome Atlas (TCGA) and performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of 18 pairs of specimens to prove the results we acquired. Among all 2695 putative eRNAs, 6 pairs of eRNA-target genes were prominently related to BCR-free survival. Growth arrest-specific protein 1 ( GAS1) was a target gene of GAS1RR ( r = 0.86, P < 0.001). Patients with low GAS1RR expression were likely to have unfavorable clinical characteristics. The result of computational Cox regression analysis demonstrated that GAS1RR may predict the prognosis of PCa independently. RT-qPCR results illuminated that GAS1RR and GAS1 were both downregulated in PCa tissues, and they show a strong positive correlation. GO and KEGG analyses revealed biological processes that GAS1RR was mainly associated with. Immune infiltration analysis indicated that GAS1RR expression is correlated with the infiltration level of six kinds of immune cells. Our results suggest that GAS1RR may be clinically useful in the prediction of PCa prognosis. Moreover, it may also be a prognostic predictor and theoretic target with great promise in PCa.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

GAS1RR, an immune-related enhancer RNA, is related to biochemical recurrence-free survival in prostate cancer

Xiong

Xiao

et al. 2022

Exp Biol Med (Maywood)

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“…Moreover, dMMR tumors also present higher expression of the metabolic immune checkpoint adenosine receptor 2A (ADORA2A) and a prominent expression of markers attributable to myelomonocytic cells (i.e., VCAM1, NLRP3, and JAK2) described to mediate MDCS expansion and accumulation [ 17 ]. These data justify combination therapies with ICIs in dMMR mPC [ 27 ].…”

Section: Immunobiology Of Prostate Cancermentioning

confidence: 91%

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

Rebuzzi

Rescigno

Catalano

et al. 2022

Cancers

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In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs.

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2020

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Elucidating Durable Responses to Immune Checkpoint Inhibition

Cited by 3 publications

References 5 publications

GAS1RR, an immune-related enhancer RNA, is related to biochemical recurrence-free survival in prostate cancer

GAS1RR, an immune-related enhancer RNA, is related to biochemical recurrence-free survival in prostate cancer

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

Pembrolizumab

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