Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Cunha, Lucas Leite; Marcello, Marjory Alana; Rocha-Santos, Vinícius; Ward, Laura Sterian

doi:10.1530/erc-17-0222

Cited by 34 publications

(22 citation statements)

References 132 publications

(156 reference statements)

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“…The signaling mechanism mediated by costimulatory/inhibitory molecules plays an important role in T cell-mediated immunity. Many cells in the TME can express ligands for inhibitory receptors on T cells, leading to their inactivation [96]. Inhibitory receptors include CTLA-4, PD-1, TIM-3, LAG-3, etc.…”

Section: Introductionmentioning

confidence: 99%

Cancer DNA vaccines: current preclinical and clinical developments and future perspectives

Lopes

Vandermeulen

Préat

2019

J Exp Clin Cancer Res

266

179

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The recent developments in immuno-oncology have opened an unprecedented avenue for the emergence of vaccine strategies. Therapeutic DNA cancer vaccines are now considered a very promising strategy to activate the immune system against cancer. In the past, several clinical trials using plasmid DNA vaccines demonstrated a good safety profile and the activation of a broad and specific immune response. However, these vaccines often demonstrated only modest therapeutic effects in clinical trials due to the immunosuppressive mechanisms developed by the tumor. To enhance the vaccine-induced immune response and the treatment efficacy, DNA vaccines could be improved by using two different strategies. The first is to increase their immunogenicity by selecting and optimizing the best antigen(s) to be inserted into the plasmid DNA. The second strategy is to combine DNA vaccines with other complementary therapies that could improve their activity by attenuating immunosuppression in the tumor microenvironment or by increasing the activity/number of immune cells. A growing number of preclinical and clinical studies are adopting these two strategies to better exploit the potential of DNA vaccination. In this review, we analyze the last 5-year preclinical studies and 10-year clinical trials using plasmid DNA vaccines for cancer therapy. We also investigate the strategies that are being developed to overcome the limitations in cancer DNA vaccination, revisiting the rationale for different combinations of therapy and the different possibilities in antigen choice. Finally, we highlight the most promising developments and critical points that need to be addressed to move towards the approval of therapeutic cancer DNA vaccines as part of the standard of cancer care in the future.

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Section: Introductionmentioning

confidence: 99%

Cancer DNA vaccines: current preclinical and clinical developments and future perspectives

Lopes

Vandermeulen

Préat

2019

J Exp Clin Cancer Res

266

179

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“…Besides, Bai Y et al found that the expression of BRAF V600E is positively correlated with PD-L1/PD-1 in PTC samples, which indicated that immune checkpoint therapy might be effective for PTC patients with the BRAF V600E mutation [24]. More importantly, several ongoing clinical trials have fueled the field of tumor immunology in thyroid cancer [25]. The thyroid gland is the largest endocrine organ in the human body, and is a frequent target of autoimmune disease.…”

Section: Introductionmentioning

confidence: 99%

Development of a prognostic index based on an immunogenomic landscape analysis of papillary thyroid cancer

Lin

Guo

Shi

et al. 2019

Aging

102

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Background: Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, and inflammation relates significantly to its initiation and prognosis. Systematic exploration of the immunogenomic landscape therein to assist in PTC prognosis is therefore urgent. The Cancer Genome Atlas (TCGA) project provides a large number of genetic PTC samples that enable a comprehensive and reliable immunogenomic study.Methods: We integrated the expression profiles of immune-related genes (IRGs) and progression-free intervals (PFIs) in survival in 493 PTC patients based on the TCGA dataset. Differentially-expressed and survival-associated IRGs in PTC patients were estimated a computational difference algorithm and COX regression analysis. The potential molecular mechanisms and properties of these PTC-specific IRGs were also explored with the help of computational biology. A new prognostic index based on immune-related genes was developed by using multivariable COX analysis.Results: A total of 46 differentially expressed immune-related genes were significantly correlated with clinical outcome of PTC patients. Functional enrichment analysis revealed that these genes were actively involved in a cytokine-cytokine receptor interaction KEGG pathway. A prognostic signature based on RGs (AGTR1, CTGF, FAM3B, IL11, IL17C, PTH2R and SPAG11A) performed moderately in prognostic predictions and correlated with age, tumor stage, metastasis, number of lesions, and tumor burden. Intriguingly, the prognostic index based on IRGs reflected infiltration by several types of immune cells.Conclusions: Together, our results screened several IRGs of clinical significance, revealed drivers of the immune repertoire, and demonstrated the importance of a personalized, IRG-based immune signature in the recognition, surveillance, and prognosis of PTC.

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“…Immune checkpoint inhibitors at the moment have the biggest role in this class since they are the novelty responsible for improving outcomes seen in other tumors such as melanoma [62]. A study of pembrolizumab in advanced solid tumors included 22 patients with advanced DTC who failed standard treatment and showed an expression of PD-L1 ≥1% or stroma cell lines by immunohistochemistry.…”

Section: Immunotherapymentioning

confidence: 99%

“…Preliminary results showed a 54.5% rate of stable disease, 9% rate of partial response, a 6-month OS rate of 100% and a 58.7% rate of 6-month PFS. Despite 18 patients had treatment-related AE, none of the patients needed to discontinue the drug [62]. At clinicaltrials.gov and EU Clinical Trials Register there are several studies ongoing with these drugs, such as ipilimumab plus nivolumab (two Phase II studies), pembrolizumab plus lenvatinib (one Phase II study), pembrolizumab alone (three Phase II studies), nivolumab alone (one Phase II study) and avelumab plus checkpoint agonist(s) with or without irradiation or irradiation plus cisplatin (one Phase I/II study).…”

Section: Immunotherapymentioning

confidence: 99%

Novel Therapies Against Aggressive Differentiated Thyroid Carcinomas

Donato¹,

Santos

Simões

et al. 2018

Int. J. Endo. Oncol.

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The incidence of thyroid cancer (TC) is increasing. Although the majority of these cancers have a good prognosis, 10% of these will develop local recurrence and/or distant metastases. Conventional cytotoxic chemotherapy has been largely replaced by molecular-target therapies, but it can still have a role. Two tyrosine kinase inhibitors have been approved for the treatment of advanced differentiated TC. They significantly improve progression-free survival, but at the cost of frequent and potentially serious adverse effects. At the moment, there are multiple clinical trials with other tyrosine kinase inhibitors and other drugs. We present a review of the current standard of care and what is up to come in the treatment of advanced TC.

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Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Cited by 34 publications

References 132 publications

Cancer DNA vaccines: current preclinical and clinical developments and future perspectives

Cancer DNA vaccines: current preclinical and clinical developments and future perspectives

Development of a prognostic index based on an immunogenomic landscape analysis of papillary thyroid cancer

Novel Therapies Against Aggressive Differentiated Thyroid Carcinomas

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