Combining BRAF inhibitor and anti PD-L1 antibody dramatically improves tumor regression and anti tumor immunity in an immunocompetent murine model of anaplastic thyroid cancer

Immune checkpoint inhibitors are agents that act by inhibiting the mechanisms of immune escape displayed by various cancers. The success of immune checkpoint inhibitors against several tumors has promoted a new treatment strategy in clinical oncology, and this has encouraged physicians to increase the number of patients who receive the immune checkpoint therapy. In the present article, we review the main concepts regarding immune checkpoint mechanisms and how cancer disrupts them to undergo immune escape. In addition, we describe the most essential concepts related to immune checkpoint inhibitors. We critically review the literature on preclinical and clinical studies of the immune checkpoint inhibitors as a treatment option for thyroid cancer, ovarian carcinoma, pancreatic adenocarcinoma, adrenocortical carcinoma and neuroendocrine tumors. We present the challenges and the opportunities of using immune checkpoint inhibitors against these endocrine malignancies, highlighting the breakthroughs and pitfalls that have recently emerged.

Section: :12mentioning

confidence: 95%

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

Cunha

Marcello

Rocha-Santos

et al. 2017

“…Moreover, the field of immunooncology has emerged in the past years and an interaction between somatic mutations and the tumor microenvironment has impressively been shown in several human malignancies (Danilova et al 2016). Whether combining targeted therapies and immune therapy in ATC patients as suggested for other advanced human malignancies and by in vivo data from preclinical thyroid cancer animal models is an effective approach which needs to be further elucidated (Brauner et al 2016).…”

Section: Targeted Therapymentioning

confidence: 99%

“…Recently, in case reports, efficacy of targeted therapy approaches has been reported. Moreover, checkpoint inhibitors might represent new treatment options (Brauner et al 2016, Latteyer et al 2016b.…”

Section: Introductionmentioning

confidence: 99%

Anaplastic thyroid carcinoma: review of treatment protocols

Tiedje¹,

Stuschke²,

Weber³

et al. 2018

Anaplastic thyroid carcinoma (ATC) is an orphan disease and in most patients fatal. So far no established treatment is available that prolongs survival. Several large retrospective studies have identified negative prognostic markers, analyzed efficacy of multimodal approaches such as radiotherapy with and without concurrent chemotherapy and chemotherapy protocols. Recently, single case reports have suggested some effectiveness of newer therapies targeting single somatic alterations in ATC. Overall, the conclusions that can be drawn from published retrospective studies and the scarce prospective approaches is that new treatment protocols should be developed including surgery, radiotherapy, chemotherapy and targeted therapy approaches and combinational therapy with immunotherapies. These protocols then need to be evaluated prospectively to improve ATC patients' outcome in routine care.

“…In such mouse models, it is now possible to evaluate the efficacy of immune checkpoint inhibitors and combined therapies for treatment of aggressive thyroid cancer. This approach has recently been shown to result in dramatically improved tumor regression under combined BRAF inhibitor and PD-L1 antibody treatment (baseline: 782.3 ± 174.6 mm 3 vs 439.3 ± 188.4 mm 3 (BRAF inhibitor) and 716.7 ± 62.1 mm 3 (PD-L1) to 147.3 ± 60.8 mm 3 with BRAF inhibitor/PD-L1 combination) (Brauner et al 2016). In addition, a very recent study from Parhar et al demonstrated the influence of IL-12 on immune response and tumor growth in BRAF V600E mice.…”

Section: :10mentioning

confidence: 99%

Perspectives for immunotherapy in endocrine cancer

Latteyer¹,

Tiedje²,

Schilling³

et al. 2016

The fight against cancer has seen major breakthroughs in recent years. More than a decade ago, tyrosine kinase inhibitors targeting constitutively activated signaling cascades within the tumor inaugurated a new era of oncological therapy. Recently, immunotherapy with immune checkpoint inhibitors has started to revolutionize the treatment of several malignancies, most notably malignant melanoma, leading to the renaissance and the long-awaited breakthrough of immunooncology. This review provides an overview of the basis of immunotherapy from its initial concepts of antitumor immunity and cell-based therapy to the development of immune checkpoint inhibitors and discusses published studies and the perspectives of immunooncology for the treatment of endocrine malignancies.