scholarly journals Electrochemotherapy as a Trigger to Overcome Primary Resistance to Anti-PD-1 Treatment: A Case Report of Melanoma of the Scalp

2021 ◽  
Vol 11 ◽  
Author(s):  
Davide Quaresmini ◽  
Alessandra Di Lauro ◽  
Livia Fucci ◽  
Sabino Strippoli ◽  
Ivana De Risi ◽  
...  
Keyword(s):  
Immune Response ◽  
Complete Remission ◽  
Checkpoint Inhibitors ◽  
Primary Resistance ◽  
Case Presentation ◽  
Palliative Intent ◽  
Good Clinical Condition ◽  
Tumor Immunogenicity ◽  
Second Procedure

BackgroundImmunotherapy with immune checkpoint inhibitors is one of the main therapies for advanced melanoma. Nevertheless, albeit remarkable, immunotherapy results are still unsatisfactory as more than half of patients progress, and resistance to treatment still has a dramatic impact on clinical outcomes. Local treatments such as radiotherapy or electrochemotherapy (ECT), in addition to local control with palliative intent, have been shown to release tumoral neoantigens that can stimulate a robust systemic antitumor immune response.Case PresentationWe report the case of a patient with multiple nodular melanoma lesions of the scalp initially treated with local ECT. Soon after the procedure, multiple new lesions appeared close to the treated ones, therefore the patient started a systemic treatment with the anti-PD-1 nivolumab. The lesions of the scalp did not respond to immunotherapy, presenting a loco-regional spreading. To control the bleeding and painful lesions, we performed a second ECT, while continuing systemic immunotherapy. The treated lesions responded to the second procedure, while the other lesions continued progressing in number and dimension. Unexpectedly, after 2 months from the second ECT, the patient presented a progressive shrinkage of both treated and untreated lesions until complete remission. Concomitantly, he developed immune-related adverse events including grade 4 thyroid toxicity, grade 2 vitiligo-like depigmentation and grade 2 pemphigoid. At present, after 18 months from the first ECT and 14 months from the starting of anti-PD-1 immunotherapy, the patient is in good clinical condition and complete remission of disease still persists.ConclusionThis case highlights the potential role of ECT in increasing tumor immunogenicity and consequently in inducing a powerful immune response overcoming primary resistance to checkpoint inhibitor immunotherapy.

9 Mesenchymal features of a novel 27-gene algorithm associate with canonical tumor promoting signaling pathways which may identify therapeutic options for immunotherapy resistant patients

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A9-A9
Author(s):  
Tyler Nielsen ◽  
Rob Seitz ◽  
Douglas Ross ◽  
David Hout ◽  
Brock Schweitzer
Keyword(s):  
Immune Response ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Pathway Analysis ◽  
Stromal Cell ◽  
Checkpoint Inhibitors ◽  
Targeted Therapeutics ◽  
Primary Resistance ◽  
Durable Response ◽  
Xenograft Models

BackgroundImmune checkpoint inhibitors have emerged as a front-line treatment for cancer in multiple indications. Unfortunately, a majority of patients do not realize durable response as a result of primary resistance to the immunotherapy. We have previously described a novel 27-gene immuno-oncology assay and algorithm which demonstrated significant predictive value in both NSCLC and TNBC. This algorithm utilizes gene expression to assess the tumor immune microenvironment (TIME) by combining aspects of the immune response, surrounding stromal cell signaling, and tumor physiology. We hypothesized that features of this algorithm may not only identify responders to immunotherapy (immunomodulatory, IO subtype) but may better enrich for patients who would benefit from other targeted therapeutics that alter the tumor microenvironment such as VEGF or FAK inhibitors (mesenchymal, M subtype).MethodsPathway analysis was used on TNBC specimens representing both the IO and M subtypes as determined by the 27-gene immuno-oncology algorithm. Expression reads were scaled within each sample and the difference of the mean of expression of each gene within IO and M subtypes was determined to quantify relative expression within each pathway. Finally, the mesenchymal score obtained from the 27-gene immuno-oncology algorithm was used to stratify RNAseq expression data from xenograft models that were either sensitive or resistant to a FAK inhibitor (FAKi).ResultsPathway analysis identified stratification between the 27-gene immuno-oncology algorithm subtypes finding with the mesenchymal subtype is associated with higher WNT, TGF-B, and RAS pathways whereas the IO subtype was more highly associated with the JAK/STAT pathway. Additionally, the mesenchymal score from the 27-gene immuno-oncology algorithm was higher in the FAK inhibitor sensitive (0.36) xenograft models than the FAKi resistant (0.076) models (p = 0.025).ConclusionsThe 27-gene immuno-oncology algorithm assesses the TIME to account for the immune response, surrounding stromal cell signaling, and tumor physiology to provide both an immuno-oncology subtype and mesenchymal subtype. We have previously demonstrated improved ability of the IO subtype to predict response to ICIs over current gold standard biomarkers. These data suggest that the M subtype is a distinct feature of the IO subtype which may enrich for patients more likely to respond to targeted therapeutics that act upon the canonical tumor promoting signaling pathways.

scholarly journals Breast Cancer Immunotherapy: An Update

2018 ◽  
Vol 12 ◽  
pp. 117822341877480 ◽  
Author(s):  
Issam Makhoul ◽  
Mohammad Atiq ◽  
Ahmed Alwbari ◽  
Thomas Kieber-Emmons
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Cancer Vaccines ◽  
Checkpoint Inhibitors ◽  
Cancer Surveillance ◽  
Cancer Disease ◽  
Immune Attack

The immune system plays a major role in cancer surveillance. Harnessing its power to treat many cancers is now a reality that has led to cures in hopeless situations where no other solutions were available from traditional anticancer drugs. These spectacular achievements rekindled the oncology community’s interest in extending the benefits to all cancers including breast cancer. The first section of this article reviews the biological foundations of the immune response to different subtypes of breast cancer and the ways cancer may overcome the immune attack leading to cancer disease. The second section is dedicated to the actual immune treatments including breast cancer vaccines, checkpoint inhibitors, monoclonal antibodies, and the “unconventional” immune role of chemotherapy.

scholarly journals The Crosstalk between Microbiome and Immune Response in Gastric Cancer

2020 ◽  
Vol 21 (18) ◽  
pp. 6586
Author(s):  
Rihab Nasr ◽  
Ali Shamseddine ◽  
Deborah Mukherji ◽  
Farah Nassar ◽  
Sally Temraz
Keyword(s):  
Gastric Cancer ◽  
Immune Response ◽  
Gut Microbiome ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Cell Responses ◽  
Host Epithelium ◽  
H Pylori

Gastric cancer is the end result of a complex interplay between host genetics, environmental factors, and microbial factors. The link between gut microbiome and gastric cancer has been attributed to persistent activation of the host’s immune system by gut microbiota. The end result of this dysregulated interaction between host epithelium and microbes is a state of chronic inflammation. Gut bacteria can promote anti-tumor immune responses through several mechanisms. These include triggering T-cell responses to bacterial antigens that can cross-react with tumor antigens or cause tumor-specific antigen recognition; engagement of pattern recognition receptors that mediate pro-immune or anti-inflammatory effects or via small metabolites that mediate systemic effects on the host. Here we review the role of the gut microbiome including H. pylori and non-H. pylori gastric bacteria, the immune response, and immunotherapy using checkpoint inhibitors. We also review the evidence for cross talk between the gut microbiome and immune response in gastric cancer.

scholarly journals The Synergistic Effect of PARP Inhibitors and Immune Checkpoint Inhibitors

2021 ◽  
Vol 15 ◽  
pp. 117955492199628
Author(s):  
Zhaozhen Wu ◽  
Pengfei Cui ◽  
Haitao Tao ◽  
Sujie Zhang ◽  
Junxun Ma ◽  
...  
Keyword(s):  
Immune Response ◽  
Dna Damage ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Parp Inhibitors ◽  
Resistance Mechanisms ◽  
Great Promise ◽  
Immunogenic Cell Death

Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated great promise for treating cancers with homologous recombination (HR) defects, such as germline BRCA1/2 mutation. Further studies suggest that PARP inhibitors (PARPi) can also exhibit efficacy in HR-competent cancers, by amplifying the DNA damage and inducing immunogenic cell death, and PARPi lead to increasing tumor neoantigen, upregulation of interferons and PD-L1, and modulation of the tumor microenvironment, which may facilitate a more profound antitumor immune response. Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 or CTLA-4 have achieved impressive success in the treatment of different malignancies. However, only a subset of populations derive clinical benefit, and the biomarkers and resistance mechanisms are not fully understood. Therefore, given that PARPi could potentiate the therapeutic effect of ICIs, PARPi combined with ICIs are becoming an alternative for patients who cannot benefit from ICI monotherapy. In this review, we focus on the mechanisms and immune role of PARPi and discuss the rationale and clinical studies of this combined regimen.

scholarly journals Immune targeted therapies for COVID-19 Infection: A Promising Outlook

2020 ◽  
Author(s):  
Bahareh Forouzani-Haghighi ◽  
Alireza Rezvani ◽  
Afsaneh Vazin
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Checkpoint Inhibitors ◽  
The Elderly ◽  
World Health ◽  
Laboratory Findings ◽  
System A ◽  
Disease Prognosis ◽  
Health Organization

In December 2019, the coronavirus disease-19 (COVID-19) outbreak emerged in Wuhan, China. On March 11, 2020, the WHO (World Health Organization) officially declared it a pandemic. Reports indicated that the associated mortality of the infection is quite higher in the elderly, patients with specific comorbidities (like diabetes mellitus), and generally the ones with a compromised immune system. A cohort study of 452 patients with laboratory-confirmed COVID-19 in Wuhan, China, reported a dysregulated immune response in these patients. As a result of this suppressed immune response, the increase of neutrophil to lymphocyte ratio (NLR), T lymphopenia, and decrease of CD4+ T cells was considered as common laboratory findings, especially in severe cases. On the other hand, there is also clear evidence of T cell exhaustion in severely ill patients. So, the immune system seems to play an important role in disease prognosis and pathogenesis. This study aims to review the evidence on the immune response dysregulation in COVID-19 infection and the potential role of immunoregulatory treatments such as immune checkpoint inhibitors, interferons, and CD200 inhibitors in altering disease prognosis, especially in critically ill patients.

scholarly journals Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II—The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer

2017 ◽  
Vol 142 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Esmeralda Celia Marginean ◽  
Barbara Melosky
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Microsatellite Instability ◽  
Therapeutic Potential ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Immune Checkpoints ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

Context.— The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti–programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability–high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability–high CRC. Objectives.— To review the immune response to cancer and the role of immune checkpoints, focusing on the technical and interpretation challenges of PD-1/programmed death ligand-1 (PD-L1) testing by pathologists and the clinical implications of the test and the therapeutic potential of treating CRC with checkpoint inhibitors. Data Sources.— A PubMed review was performed of articles pertaining to CRC, microsatellite instability and mismatch repair systems, molecular classification, immune response, PD-1/PD-L1, and immunotherapy. Conclusions.— Exciting success with anti–PD-1/PD-L1 and anticytotoxic T-lymphocyte–associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability–high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint blockades with anti–PD-1 or anti–PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability–high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls.

scholarly journals Mechanisms of immune evasion in bladder cancer

2019 ◽  
Vol 69 (1) ◽  
pp. 3-14 ◽  
Author(s):  
Paul L. Crispen ◽  
Sergei Kusmartsev
Keyword(s):  
Immune Response ◽  
Bladder Cancer ◽  
Tumor Microenvironment ◽  
Immune Evasion ◽  
Cancer Biology ◽  
Checkpoint Inhibitors ◽  
New Agents ◽  
Multiple Trials ◽  
Checkpoint Inhibitor Therapy

AbstractWith the introduction of multiple new agents, the role of immunotherapy is rapidly expanding across all malignancies. Bladder cancer is known to be immunogenic and is responsive to immunotherapy including intravesical BCG and immune checkpoint inhibitors. Multiple trials have addressed the role of checkpoint inhibitors in advanced bladder cancer, including atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab (all targeting the PD1/PD-L1 pathway). While these trials have demonstrated promising results and improvements over existing therapies, less than half of patients with advanced disease demonstrate clinical benefit from checkpoint inhibitor therapy. Recent breakthroughs in cancer biology and immunology have led to an improved understanding of the influence of the tumor microenvironment on the host’s immune system. It appears that tumors promote the formation of highly immunosuppressive microenvironments preventing generation of effective anti-tumor immune response through multiple mechanisms. Therefore, reconditioning of the tumor microenvironment and restoration of the competent immune response is essential for achieving optimal efficacy of cancer immunotherapy. In this review, we aim to discuss the major mechanisms of immune evasion in bladder cancer and highlight novel pathways and molecular targets that may help to attenuate tumor-induced immune tolerance, overcome resistance to immunotherapy and improve clinical outcomes.

scholarly journals Topical and intralesional therapies for in-transitmelanoma

2019 ◽  
Vol 6 (3) ◽  
pp. MMT23 ◽  
Author(s):  
Michael A Henderson
Keyword(s):  
Immune Response ◽  
Mechanism Of Action ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Surgical Excision ◽  
Local Immune Response ◽  
Talimogene Laherparepvec ◽  
In Transit ◽  
Local Surgical Excision

This report surveys the role of topical and intralesional agents in the management of in-transit melanoma. The extent and progression of in-transit disease is highly variable and many patients can have a protracted period of locoregional control. These agents are useful in the management of patients who have progressed beyond local surgical excision in whom more aggressive therapies, such as isolated limb infusion or use of talimogene laherparepvec, are not appropriate or have failed. In general, these agents are modestly effective and associated with frequent but only minor toxicity. As the mechanism of action of many of these agents includes initiation of a local immune response, combinations with immune checkpoint inhibitors are currently being explored.

scholarly journals miRNA as a Modulator of Immunotherapy and Immune Response in Melanoma

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1648
Author(s):  
Mai-Huong Thi Nguyen ◽  
Yueh-Hsia Luo ◽  
An-Lun Li ◽  
Jen-Chieh Tsai ◽  
Kun-Lin Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Applicability ◽  
Melanoma Patients

Immune checkpoint inhibitors are a promising therapy for the treatment of cancers, including melanoma, that improved benefit clinical outcomes. However, a subset of melanoma patients do not respond or acquire resistance to immunotherapy, which limits their clinical applicability. Recent studies have explored the reasons related to the resistance of melanoma to immune checkpoint inhibitors. Of note, miRNAs are the regulators of not only cancer progression but also of the response between cancer cells and immune cells. Investigation of miRNA functions within the tumor microenvironment have suggested that miRNAs could be considered as key partners in immunotherapy. Here, we reviewed the known mechanism by which melanoma induces resistance to immunotherapy and the role of miRNAs in immune responses and the microenvironment.

Predictive markers of immune response in glioblastoma: hopes and facts

2020 ◽  
Vol 16 (15) ◽  
pp. 1053-1063 ◽  
Author(s):  
Vincenzo Di Nunno ◽  
Enrico Franceschi ◽  
Lidia Gatto ◽  
Stefania Bartolini ◽  
Alba Ariela Brandes
Keyword(s):  
Immune Response ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Predictive Markers ◽  
Advanced Solid Tumors ◽  
Critical Importance

Immune-checkpoint inhibitors (ICI) represent a concrete hope for patients with advanced solid tumors. Indeed, patients responding to these agents may experience a long-lasting response. Recently, results of interventional clinical trials investigated the role of ICIs in patients with glioblastoma. Results of these studies suggested that only a small percentage of these patients could benefit from these agents. Research of predictive markers assumes a critical importance to adequately select patients likely to benefit from ICIs. Molecular and clinical variables associated to tumors and patients have been evaluated as potential predictive markers. Main aim of the current work is to summarize and critically evaluate current knowledge in this field.

Sign in / Sign up

Export Citation Format

Share Document