Review of cancer treatment with immune checkpoint inhibitors

Thallinger, Christiane; Füreder, Thorsten; Preusser, Matthias; Heller, Gerwin; Müllauer, Leonhard; Höller, Christoph; Prosch, Helmut; Frank, Natalija; Świerzewski, Rafał; Berger, Walter; Jäger, Ulrich; Zielinski, Christoph

doi:10.1007/s00508-017-1285-9

Cited by 109 publications

(71 citation statements)

References 62 publications

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“…Recognizing that the RANKL/RANK pathway has a multifactorial effect in the immune system and might be modulated in several ways, the antitumor immunity led to evaluating the potential role of RANKL inhibitors in improving the efficacy of ICIs in the treatment of cancer [ 81 , 82 ].…”

Section: Coinhibition Of Rankl and Immune Checkpoint Inhibitors (Imentioning

confidence: 99%

The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL

Simatou

Sarantis

Koustas

et al. 2020

IJMS

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The receptor activator of nuclear factor-κB (RANK) and the RANK ligand (RANKL) were reported in the regulation of osteoclast differentiation/activation and bone homeostasis. Additionally, the RANKL/RANK axis is a significant mediator of progesterone-driven mammary epithelial cell proliferation, potentially contributing to breast cancer initiation and progression. Moreover, several studies supported the synergistic effect of RANK and epidermal growth factor receptor (EGFR) and described RANK’s involvement in epidermal growth factor receptor 2 (ERBB2)-positive carcinogenesis. Consequently, anti-RANKL treatment has been proposed as a new approach to preventing and treating breast cancer and metastases. Recently, RANKL/RANK signaling pathway inhibition has been shown to modulate the immune environment and enhance the efficacy of anti-CTLA-4 and anti-PD-1 monoclonal antibodies against solid tumors. Clinical and experimental trials have emerged evaluating RANKL inhibition as an enhancer of the immune response, rendering resistant tumors responsive to immune therapies. Trials evaluating the combinatorial effect of immune checkpoint inhibitors and anti-RANKL treatment in double-positive (RANK+/ERBB2+) patients are encouraging.

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Section: Coinhibition Of Rankl and Immune Checkpoint Inhibitors (Imentioning

confidence: 99%

The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL

Simatou

Sarantis

Koustas

et al. 2020

IJMS

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“…The clinical successes of blocking antibodies that target the braking mechanisms employed by tumors have established the use of immunotherapy as a powerful therapeutic tool to improve patient survival. However, the currently approved drugs targeting the immunosuppressive PD-1/PD-L1 or CTLA-4 axes, while efficacious in some [1,2], do not adequately address the realm of alterations that occur in tumors or the local microenvironment to suppress an anti-tumor immune response [3,4].…”

Section: Introductionmentioning

confidence: 99%

The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors

Konen

Fradette

Gibbons

2019

Cells

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The regulation of the immune microenvironment within solid tumors has received increasing attention with the development and clinical success of immune checkpoint blockade therapies, such as those that target the PD-1/PD-L1 axis. The metabolic microenvironment within solid tumors has proven to be an important regulator of both the natural suppression of immune cell functionality and the de novo or acquired resistance to immunotherapy. Enzymatic proteins that generate immunosuppressive metabolites like adenosine are thus attractive targets to couple with immunotherapies to improve clinical efficacy. CD38 is one such enzyme. While the role of CD38 in hematological malignancies has been extensively studied, the impact of CD38 expression within solid tumors is largely unknown, though most current data indicate an immunosuppressive role for CD38. However, CD38 is far from a simple enzyme, and there are several remaining questions that require further study. To effectively treat solid tumors, we must learn as much about this multifaceted protein as possible—i.e., which infiltrating immune cell types express CD38 for functional activities, the most effective CD38 inhibitor(s) to employ, and the influence of other similarly functioning enzymes that may also contribute towards an immunosuppressive microenvironment. Gathering knowledge such as this will allow for intelligent targeting of CD38, the reinvigoration of immune functionality and, ultimately, tumor elimination.

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“…Считается, что развитие иоНР является результатом аутореактивного иммунного ответа в отношении здоровых тканей вследствие избыточной стимуляции иммунологической реактивности (гиперактивация Т-лимфоцитов, В-лимфоцитов и высвобождение цитокинов) [62][63][64][65].…”

Section: анализ нежелательных реакций связанных с применением ингибиunclassified

Immune Response Checkpoint Inhibitors: New Risks of a New Class of Antitumor Agents

Шубникова¹,

Букатина²,

Вельц³

et al. 2020

Bezopasnost' i risk farmakoterapii

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The introduction into clinical practice of immune checkpoint inhibitors that block cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand-1 (PD-L1), has improved the prognosis of patients with malignant neoplasms of diﬀ erent localisation. The antitumour eﬀ ect of immune checkpoint inhibitors is based on blocking CTLA-4 and PD-1/PD-L1 signaling pathways and enhancing lymphocyte antitumour activity. However, inhibition of immune checkpoints may lead to dysregulation of immune responses and appearance of a new type of adverse reactions resulting from changes in the activity of immunocompetent cells. The aim of the study was to analyse adverse reactions associated with the use of immune checkpoint inhibitors. It was demonstrated that the structure of immune-mediated adverse reactions varied depending on the class of immune checkpoint inhibitors. The incidence of immune-mediated adverse reactions was higher with CTLA-4 inhibitors as compared with PD-1/PD-L1 inhibitors, and increased signiﬁ cantly in the case of combination therapy. The treatment with CTLA-4 inhibitors most often resulted in skin reactions (rash, itching), gastrointestinal tract reactions (diarrhea, colitis), and endocrine gland problems (hypophysitis). The treatment with PD-1 inhibitors most often led to respiratory disorders (pneumonitis), and in some cases to gastrointestinal disorders (diarrhea, colitis), skin reactions (rash, itching), and endocrine gland problems (hypothyroidism), but they were less common. The treatment with PD-L1 inhibitors was associated with the development of pneumonitis. The development of immune-mediated adverse reactions may require discontinuation of treatment and administration of immunosuppressants, therefore early diagnosis and timely treatment of complications are important prerequisites for successful antitumour therapy. Further study of the mechanisms of immune-mediated adverse reaction development will optimise antitumour therapy with immune checkpoint inhibitors.

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Review of cancer treatment with immune checkpoint inhibitors

Cited by 109 publications

References 62 publications

The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL

The Role of the RANKL/RANK Axis in the Prevention and Treatment of Breast Cancer with Immune Checkpoint Inhibitors and Anti-RANKL

The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors

Immune Response Checkpoint Inhibitors: New Risks of a New Class of Antitumor Agents

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