Cancers, Vol. 12, Pages 804: Hyperprogression Under Immune Checkpoint-Based Immunotherapy —Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model

Cancers, Vol. 12, Pages 804: Hyperprogression Under Immune Checkpoint-Based Immunotherapy—Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model Cancers doi: 10.3390/cancers12040804 Authors: Kocikowski Dziubek Parys Immune evasion is a major challenge for the development of successful cancer treatments. One of the known mechanisms is the expression of immune checkpoints (ICs)—proteins regulating the immune cells activation. The advent of immunotherapy using monoclonal antibodies (mAbs) to block the immune checkpoint receptor-ligand interaction brought about a landslide improvement in the treatment responses, leading to a prompt approval of such therapeutics. In recent years, it was discovered that a subset of patients receiving IC blockade treatment experienced a previously unknown pattern of treatment response called hyperprogression (HP), characterised by rapid deterioration on initialisation of the therapy. HP represents an urgent issue for clinicians and drug developers, while posing questions about the adequacy of the current clinical trial process. Here, we briefly summarise the state of knowledge and propose new directions for research into HP mechanisms, focusing on tumour-intrinsic signalling of IC proteins malignantly expressed by cancer. We also discuss the potential role of spontaneously occurring canine cancer in the assessment of immunotherapeutics, which can ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research

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Purpose of review There are several first-line systemic therapy options for patients with newly diagnosed stage IV non-small-cell lung cancer. Targeted therapy with tyrosine kinase inhibitors provide a good first option for some. Unfortunately, most patients do not have an alteration for which there is an available tyrosine kinase inhibitor. For these patients there are immunotherapy and chemoimmunotherapy options; however, there is debate about how to choose amongst these treatments for a given individual. This review attempts to simplify this decision-making process. Recent findings The data on first-line immunother...
Source: Current Opinion in Pulmonary Medicine - Category: Respiratory Medicine Tags: NEOPLASMS OF THE LUNG: Edited by Alan M. Fein and David E. Ost Source Type: research
Rationale: Pulmonary sarcomatoid carcinoma (PSC) is an uncommon type of non-small cell lung cancer, exhibiting aggressive behavior and resistance to the conventional chemoradiotherapy. To date, the optimal treatment for PSC has not been elucidated. Patient concerns: Three male patients including a 69-year-old smoker (Case 1), a 45-year-old non-smoker (Case 2), and a 69-year-old smoker (Case 3) were admitted because of cough, back pain, and loss of body weight respectively. Diagnoses: Radiographical examinations in these patients showed bulky intrathoracic lesions, which were pathologically diagnosed as PSC staging ...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
AbstractAKT-inhibition is a promising approach to improve T cell therapies; however, its effect on CD4+ T cells is insufficiently explored. Previously, we and others showed that AKT-inhibition during ex vivo CD8+ T cell expansion facilitates the generation of polyfunctional T cells with stem cell memory-like traits. However, most therapeutic T cell products are generated from lymphocytes, containing CD4+ T cells that can affect CD8+ T cells dependent on the Th-subset. Here, we investigated the effect of AKT-inhibition on CD4+ T cells, during separate as well as total T cell expansions. Interestingly, ex vivo AKT-inhibition...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
iki Karachaliou Rafael Rosell Treatment of advanced (metastatic) non-small-cell lung cancer (NSCLC) is currently mainly based on immunotherapy with antibodies against PD-1 or PD-L1, alone, or in combination with chemotherapy. In locally advanced NSCLC and in early resected stages, immunotherapy is also employed. Tumor PD-L1 expression by immunohistochemistry is considered the standard practice. Response rate is low, with median progression free survival very short in the vast majority of studies reported. Herein, numerous biological facets of NSCLC are described involving driver genetic lesions, mutations ad fusions,...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Yu-Tzu Tai The treatment of multiple myeloma (MM) has entered into a new era of immunotherapy. Novel immunotherapies will significantly improve patient outcome via simultaneously targeting malignant plasma cell (PC) and reversing immunocompromised bone marrow (BM) microenvironment. B-cell maturation antigen (BCMA), selectively expressed in PCs and a key receptor for A proliferation-inducing ligand (APRIL), is highly expressed in MM cells from patients at all stages. The APRIL/BCMA signal cascades promote the survival and drug resistance of MM cells and further modulate immunosuppressive BM milieu. Impressively, anti...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
AbstractPurpose of ReviewThis review summarizes the role of the microbiome in colorectal cancer (CRC) in the setting of immunotherapy and emphasizes the potential of microbiota-influencing strategies with a focus on the use of fecal microbiota transplant (FMT).Recent FindingsObservations from preclinical and clinical studies suggest that the human gut microbiome is implicated in the CRC carcinogenesis and is integral in determining the clinical response and toxicity to immunotherapy. Among the therapeutic methods devised to exploit the microbiome, FMT is the most direct method and is backed by the highest level of evidence...
Source: Current Colorectal Cancer Reports - Category: Cancer & Oncology Source Type: research
(American Association for the Advancement of Science) By analyzing 442 samples from three groups of children and adults with acute myeloid leukemia (AML), researchers have identified new immune classes of the disease that predict the likelihood of drug resistance and positive responses to immunotherapy.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
In conclusion, S-588410 induces a tumor immune response in esophageal cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 antibodies may offer a clinically useful therapy.Trial registration UMIN-CTR registration identifier: UMIN000023324.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
AbstractThe tumor microenvironment (TME) not only facilitates cancer progression from the early formation to distant metastasis, but also it differs itself from time to time alongside the tumor evolution. Tumor-associated macrophages (TAMs), whether as pre-existing tissue-resident macrophages or recruited monocytes, are an inseparable part of this microenvironment. As their parents are broadly classified into a dichotomic, simplistic M1 and M2 subtypes, TAMs also exert paradoxical and diverse phenotypes as they are settled in different regions of TME and receive different microenvironmental signals. Briefly, M1 macrophages...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Immunotherapy has achieved long-term disease control in a proportion of cancer patients, but determinants of clinical benefit remain unclear. A greater understanding of antitumor immunity on an individual basis is needed to facilitate a precision oncology approach. A conceptual framework called the “cancer-immune set point” has been proposed to describe the equilibrium between factors that promote or suppress anticancer immunity and can serve as a basis to understand the variability in clinical response to immune checkpoint blockade. Oesophageal cancer has a high mutational burden, develops from pre-existing ch...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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