scholarly journals Mathematical modelling of autoimmune myocarditis and the effects of immune checkpoint inhibitors

2021 ◽  
Author(s):  
Solveig A. van der Vegt ◽  
Liudmila Polonchuk ◽  
Ken Wang ◽  
Sarah L. Waters ◽  
Ruth E. Baker
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Predictive Modelling ◽  
Cancer Therapies ◽  
Autoimmune Myocarditis ◽  
Treatment Regimens ◽  
Disease Characteristics ◽  
Bifurcation Structures

AbstractAutoimmune myocarditis is a rare, but frequently fatal, side effect of immune checkpoint inhibitors (ICIs), a class of cancer therapies. Despite extensive experimental work on the causes, development and progression of this disease, much still remains unknown about the importance of the different immunological pathways involved. We present a mathematical model of autoimmune myocarditis and the effects of ICIs on its development and progression to either resolution or chronic inflammation. From this, we gain a better understanding of the role of immune cells, cytokines and other components of the immune system in driving the cardiotoxicity of ICIs. We parameterise the model using existing data from the literature, and show that qualitative model behaviour is consistent with disease characteristics seen in patients in an ICI-free context. The bifurcation structures of the model show how the presence of ICIs increases the risk of developing autoimmune myocarditis. This predictive modelling approach is a first step towards determining treatment regimens that balance the benefits of treating cancer with the risk of developing autoimmune myocarditis.

Gastroenteropancreatic Neuroendocrine Neoplasms (GEP NENs) : The Role of Checkpoint Inhibitors

2022 ◽  
Vol 22 ◽  
Author(s):  
Giulia Arrivi ◽  
Nicola Fazio
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Response Assessment ◽  
Neuroendocrine Neoplasms ◽  
Precision Oncology ◽  
Disease Characteristics

Background: The treatment options for GEP-NENs includes various drugs and is based on grading, morphology and location of the primary Objective: The aim of our work is to investigate the clinical impact of new immune checkpoint inhibitors in order to define a new possible strategy of use within GEP-NENs. Method: A scientific literature search from 2015 to January 2020 was performed by using PubMed and Embase: reviews and prospective or retrospective studies with a minimum of twenty patients were selected; conference proceedings were included Results: several studies have been conducted to assess the role of immune checkpoint inhibitors in NENs, but nowadays the current knowledge in this field is mainly based on a phase I-II studies. Immunotherapy showed limited antitumor activity, but higher response rate was reported in poor-differentiated neuroendocrine tumors. No specific biomarkers were identified for patient selection and response assessment Conclusion: Immunotherapy appears as a powerful possibility to help our patients, but nowadays we see many gaps in this field. We must balance therapeutic possibility offered by precision oncology with the understanding the limitations of application of testing and treatment in clinical practice. Future efforts should focus on research of the best patients to candidate for immunotherapy in term of disease characteristics and previous treatments, and how to select them with accurate biomarkers.

scholarly journals P09.25 Role of Immune Checkpoint Inhibitors (ICPi) in KRAS-Mutated Non-Small Cell Lung Cancer (NSCLC)

2021 ◽  
Vol 16 (3) ◽  
pp. S300-S301
Author(s):  
M. Peravali ◽  
C. Gomes-Lima ◽  
E. Tefera ◽  
M. Baker ◽  
M. Sherchan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110244
Author(s):  
Vanessa Wookey ◽  
Axel Grothey
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Standard Of Care ◽  
Cancer Type ◽  
Cancer Therapies ◽  
Multiple Cancer ◽  
Multiple Treatment

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

scholarly journals Targeting macrophages in cancer immunotherapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhaojun Duan ◽  
Yunping Luo
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Strategies ◽  
Cellular Immunotherapy ◽  
Cancer Therapies ◽  
Tumor Vaccines ◽  
Development And Differentiation ◽  
Promising Treatment ◽  
Cancer Immunotherapies

AbstractImmunotherapy is regarded as the most promising treatment for cancers. Various cancer immunotherapies, including adoptive cellular immunotherapy, tumor vaccines, antibodies, immune checkpoint inhibitors, and small-molecule inhibitors, have achieved certain successes. In this review, we summarize the role of macrophages in current immunotherapies and the advantages of targeting macrophages. To better understand and make better use of this type of cell, their development and differentiation characteristics, categories, typical markers, and functions were collated at the beginning of the review. Therapeutic strategies based on or combined with macrophages have the potential to improve the treatment efficacy of cancer therapies.

scholarly journals A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics

2021 ◽  
Author(s):  
Jie Zhang ◽  
Zhujiang Dai ◽  
Cheng Yan ◽  
Wenjie Zhang ◽  
Daorong Wang ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Epidemiological Studies ◽  
Term Survival ◽  
Checkpoint Inhibitor Therapy ◽  
Rational Use Of Antibiotics

AbstractCancer immunotherapy has revolutionized the treatment of many malignant tumors. Although immune checkpoint inhibitors (ICIs) can reactivate the anti-tumor activity of immune cells, sensitivity to immune checkpoint inhibitor therapy depends on the complex tumor immune processes. In recent years, numerous researches have demonstrated the role of intestinal microbiota in immunity and metabolism of the tumor microenvironment, as well as the efficacy of immunotherapy. Epidemiological studies have further demonstrated the efficacy of antibiotic therapy on the probability of patients' response to ICIs and predictability of the short-term survival of cancer patients. Disturbance to the intestinal microbiota significantly affects ICIs-mediated immune reconstitution and is considered a possible mechanism underlying the development of adverse effects during antibiotic-based ICIs treatment. Intestinal microbiota, antibiotics, and ICIs have gradually become important considerations for the titer of immunotherapy. In the case of immunotherapy, the rational use of antibiotics and intestinal microbiota is expected to yield a better prognosis for patients with malignant tumors.

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.

scholarly journals Rethinking immune checkpoint blockade: ‘Beyond the T cell’

2021 ◽  
Vol 9 (1) ◽  
pp. e001460 ◽  
Author(s):  
Xiuting Liu ◽  
Graham D Hogg ◽  
David G DeNardo
Keyword(s):  
Immune System ◽  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Antitumor Immunity ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade

The clinical success of immune checkpoint inhibitors has highlighted the central role of the immune system in cancer control. Immune checkpoint inhibitors can reinvigorate anti-cancer immunity and are now the standard of care in a number of malignancies. However, research on immune checkpoint blockade has largely been framed with the central dogma that checkpoint therapies intrinsically target the T cell, triggering the tumoricidal potential of the adaptive immune system. Although T cells undoubtedly remain a critical piece of the story, mounting evidence, reviewed herein, indicates that much of the efficacy of checkpoint therapies may be attributable to the innate immune system. Emerging research suggests that T cell-directed checkpoint antibodies such as anti-programmed cell death protein-1 (PD-1) or programmed death-ligand-1 (PD-L1) can impact innate immunity by both direct and indirect pathways, which may ultimately shape clinical efficacy. However, the mechanisms and impacts of these activities have yet to be fully elucidated, and checkpoint therapies have potentially beneficial and detrimental effects on innate antitumor immunity. Further research into the role of innate subsets during checkpoint blockade may be critical for developing combination therapies to help overcome checkpoint resistance. The potential of checkpoint therapies to amplify innate antitumor immunity represents a promising new field that can be translated into innovative immunotherapies for patients fighting refractory malignancies.

scholarly journals Role of Immune Checkpoint Inhibitors in Cervical Cancer: From Preclinical to Clinical Data

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2089
Author(s):  
Simona Duranti ◽  
Antonella Pietragalla ◽  
Gennaro Daniele ◽  
Camilla Nero ◽  
Francesca Ciccarone ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Hpv Infection ◽  
Phase Iii ◽  
Screening Programs ◽  
Cervical Cancers ◽  
Relapsed Disease

Human papillomavirus (HPV) infection is the recognized cause of almost all cervical cancers. Despite the reduction in incidence due to a wide use of screening programs and a specific vaccine, the prognosis of cervical cancer remains poor, especially for late-stage and relapsed disease. Considering the elevated rates of PD-L1 expression in up to 80% of cervical cancers, a strong rationale supports the use of immunotherapy to restore the immune response against tumor. The aim of this review is to analyze the possible role of immune checkpoint inhibitors in cervical cancer treatment, with a particular focus on the rationale and on the results of phase I and II clinical trials. An overview of ongoing phase III studies with possible future areas of development is also provided.

scholarly journals Is There a Place for Immune Checkpoint Inhibitors in Vulvar Neoplasms? A State of the Art Review

2020 ◽  
Vol 22 (1) ◽  
pp. 190
Author(s):  
Fulvio Borella ◽  
Mario Preti ◽  
Luca Bertero ◽  
Giammarco Collemi ◽  
Isabella Castellano ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
State Of The Art ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Survival Rates ◽  
Younger Women ◽  
Multiple Tumor ◽  
Tumor Types

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.

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