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Cellular & Molecular Immunology Aug 2020Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types of immunotherapy, including adoptive cell transfer (ACT)... (Review)
Review
Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types of immunotherapy, including adoptive cell transfer (ACT) and immune checkpoint inhibitors (ICIs), have obtained durable clinical responses, but their efficacies vary, and only subsets of cancer patients can benefit from them. Immune infiltrates in the tumor microenvironment (TME) have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients. Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer-immune evasion, thus providing opportunities for the development of novel therapeutic strategies. However, the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells. With recent advances in single-cell technologies such as single-cell RNA sequencing (scRNA-seq) and mass cytometry, systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells. In this review, we outline the recent progress in cancer immunotherapy, particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells, and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy. We believe such a review could strengthen our understanding of the progress in cancer immunotherapy, facilitate the elucidation of immune cell modulation in tumor progression, and thus guide the development of novel immunotherapies for cancer treatment.
Topics: Cancer Vaccines; History, 19th Century; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Neoplasms; Single-Cell Analysis
PubMed: 32612154
DOI: 10.1038/s41423-020-0488-6 -
European Review For Medical and... Jun 2018This is a review regarding different types of cancer treatments. We aimed at analyzing the tumor microenvironment and the recent trends for the therapeutic applications... (Review)
Review
This is a review regarding different types of cancer treatments. We aimed at analyzing the tumor microenvironment and the recent trends for the therapeutic applications and effectiveness for several kinds of cancers. Traditionally the cancer treatment was based on the neoplastic cells. Methods such as surgery, radiation, chemotherapy, and immunotherapy, which were targeted on the highly proliferating mutated tumor cells, have been investigated. The tumor microenvironment describes the non-cancerous cells in the tumor and has enabled to investigate the behavior and response of the cancer cells to a treatment process; it consists in a tissue that may have a predictive significance for tumor behavior and response to therapy. These include fibroblasts, immune cells and cells that comprise the blood vessels. It also includes the proteins produced by all of the cells present in the tumor that support the growth of the cancer cells. By monitoring changes in the tumor microenvironment using its molecular and cellular profiles as the tumor progresses will be vital for identifying cell or protein targets for the cancer prevention and its therapeutic purposes.
Topics: Antineoplastic Agents; Cell Communication; Humans; Immunotherapy; Neoplasm Metastasis; Neoplasms; Radiation, Ionizing; Tumor Microenvironment
PubMed: 29949179
DOI: 10.26355/eurrev_201806_15270 -
Nature Reviews. Drug Discovery Mar 2019Immunotherapy has become a powerful clinical strategy for treating cancer. The number of immunotherapy drug approvals has been increasing, with numerous treatments in... (Review)
Review
Immunotherapy has become a powerful clinical strategy for treating cancer. The number of immunotherapy drug approvals has been increasing, with numerous treatments in clinical and preclinical development. However, a key challenge in the broad implementation of immunotherapies for cancer remains the controlled modulation of the immune system, as these therapeutics have serious adverse effects including autoimmunity and nonspecific inflammation. Understanding how to increase the response rates to various classes of immunotherapy is key to improving efficacy and controlling these adverse effects. Advanced biomaterials and drug delivery systems, such as nanoparticles and the use of T cells to deliver therapies, could effectively harness immunotherapies and improve their potency while reducing toxic side effects. Here, we discuss these research advances, as well as the opportunities and challenges for integrating delivery technologies into cancer immunotherapy, and we critically analyse the outlook for these emerging areas.
Topics: Animals; Drug Delivery Systems; Humans; Immunotherapy; Nanoparticles; Neoplasms; T-Lymphocytes
PubMed: 30622344
DOI: 10.1038/s41573-018-0006-z -
Trends in Cancer Jun 2018Pancreatic cancer is the third-leading cause of cancer mortality in the USA, recently surpassing breast cancer. A key component of pancreatic cancer's lethality is its... (Review)
Review
Pancreatic cancer is the third-leading cause of cancer mortality in the USA, recently surpassing breast cancer. A key component of pancreatic cancer's lethality is its acquired immune privilege, which is driven by an immunosuppressive microenvironment, poor T cell infiltration, and a low mutational burden. Although immunotherapies such as checkpoint blockade or engineered T cells have yet to demonstrate efficacy, a growing body of evidence suggests that orthogonal combinations of these and other strategies could unlock immunotherapy in pancreatic cancer. In this Review article, we discuss promising immunotherapies currently under investigation in pancreatic cancer and provide a roadmap for the development of prevention vaccines for this and other cancers.
Topics: Cancer Vaccines; Humans; Immunotherapy; Pancreatic Neoplasms
PubMed: 29860986
DOI: 10.1016/j.trecan.2018.04.001 -
CA: a Cancer Journal For Clinicians Mar 2020Cancer immunotherapies, including checkpoint inhibitors and adoptive cell therapy, manipulate the immune system to recognize and attack cancer cells. These therapies... (Review)
Review
Cancer immunotherapies, including checkpoint inhibitors and adoptive cell therapy, manipulate the immune system to recognize and attack cancer cells. These therapies have the potential to induce durable responses in multiple solid and hematologic malignancies and thus have transformed treatment algorithms for numerous tumor types. Cancer immunotherapies lead to unique toxicity profiles distinct from the toxicities of other cancer therapies, depending on their mechanism of action. These toxicities often require specific management, which can include steroids and immune-modulating therapy and for which consensus guidelines have been published. This review will focus on the toxicities of checkpoint inhibitors and chimeric antigen receptor T cells, including pathophysiology, diagnosis, and management.
Topics: Humans; Immunologic Factors; Immunotherapy; Neoplasms
PubMed: 31944278
DOI: 10.3322/caac.21596 -
Critical Reviews in Clinical Laboratory... 2009Recent scientific advances have expanded our understanding of the immune system and its response to malignant cells. The clinical goal of tumour immunotherapy is to... (Review)
Review
Recent scientific advances have expanded our understanding of the immune system and its response to malignant cells. The clinical goal of tumour immunotherapy is to provide either passive or active immunity against malignancies by harnessing the immune system to target tumours. Monoclonal antibodies, cytokines, cellular immunotherapy, and vaccines have increasingly become successful therapeutic agents for the treatment of solid and haematological cancers in preclinical models, clinical trials, and practice. In this article, we review recent advances in the immunotherapy of cancer, focusing on new strategies and future perspectives as well as on clinical trials attempting to enhance the efficacy of immunotherapeutic modalities and translate this knowledge into effective cancer therapies.
Topics: Animals; Humans; Immunotherapy; Neoplasms
PubMed: 19650714
DOI: 10.1080/10408360902937809 -
Nature Reviews. Clinical Oncology Jan 2021TGFβ signalling has key roles in cancer progression: most carcinoma cells have inactivated their epithelial antiproliferative response and benefit from increased TGFβ... (Review)
Review
TGFβ signalling has key roles in cancer progression: most carcinoma cells have inactivated their epithelial antiproliferative response and benefit from increased TGFβ expression and autocrine TGFβ signalling through effects on gene expression, release of immunosuppressive cytokines and epithelial plasticity. As a result, TGFβ enables cancer cell invasion and dissemination, stem cell properties and therapeutic resistance. TGFβ released by cancer cells, stromal fibroblasts and other cells in the tumour microenvironment further promotes cancer progression by shaping the architecture of the tumour and by suppressing the antitumour activities of immune cells, thus generating an immunosuppressive environment that prevents or attenuates the efficacy of anticancer immunotherapies. The repression of TGFβ signalling is therefore considered a prerequisite and major avenue to enhance the efficacy of current and forthcoming immunotherapies, including in tumours comprising cancer cells that are not TGFβ responsive. Herein, we introduce the mechanisms underlying TGFβ signalling in tumours and their microenvironment and discuss approaches to inhibit these signalling mechanisms as well as the use of these approaches in cancer immunotherapies and their potential adverse effects.
Topics: Animals; Disease Progression; Humans; Immunotherapy; Neoplasms; Signal Transduction; Transforming Growth Factor beta
PubMed: 32710082
DOI: 10.1038/s41571-020-0403-1 -
Frontiers in Immunology 2023Immunotherapy has ushered in a new era in cancer treatment, and cancer immunotherapy continues to be rejuvenated. The clinical goal of cancer immunotherapy is to prime... (Review)
Review
Immunotherapy has ushered in a new era in cancer treatment, and cancer immunotherapy continues to be rejuvenated. The clinical goal of cancer immunotherapy is to prime host immune system to provide passive or active immunity against malignant tumors. Tumor infiltrating leukocytes (TILs) play an immunomodulatory role in tumor microenvironment (TME) which is closely related to immune escape of tumor cells, thus influence tumor progress. Several cancer immunotherapies, include immune checkpoint inhibitors (ICIs), cancer vaccine, adoptive cell transfer (ACT), have shown great efficacy and promise. In this review, we will summarize the recent research advances in tumor immunotherapy, including the molecular mechanisms and clinical effects as well as limitations of immunotherapy.
Topics: Immunotherapy; Immunomodulation; Immunity, Active; Immunotherapy, Adoptive; Adoptive Transfer; Neoplasms
PubMed: 37691932
DOI: 10.3389/fimmu.2023.1212476 -
Clinical Cancer Research : An Official... Jul 2023Despite revolutionizing cancer management, immunotherapies dysregulate the immune system, leading to immune-mediated adverse events. These common and potentially... (Review)
Review
Despite revolutionizing cancer management, immunotherapies dysregulate the immune system, leading to immune-mediated adverse events. These common and potentially dangerous toxicities are often treated with corticosteroids, which are among the most prescribed drugs in oncology for a wide range of cancer and noncancer indications. While steroids exert several mechanisms to reduce immune activity, immunotherapies, such as immune checkpoint inhibitors (ICI), are designed to enhance the immune system's inherent antitumor activity. Because ICI requires an intact and robust immune response, the immunosuppressive properties of steroids have led to a widespread concern that they may interfere with antitumor responses. However, the existing data of the effect of systemic steroids on immunotherapy efficacy remain somewhat conflicted and unclear. To inform clinical decision-making and improve outcomes, we review the impact of steroids on antitumor immunity, recent advances in the knowledge of their impact on ICI efficacy in unique populations and settings, associated precautions, and steroid-sparing treatment approaches.
Topics: Humans; Neoplasms; Immunosuppressive Agents; Adrenal Cortex Hormones; Immunotherapy
PubMed: 36648402
DOI: 10.1158/1078-0432.CCR-22-3181 -
Journal of Immunology Research 2020Until now, three types of well-recognized cancer treatments have been developed, i.e., surgery, chemotherapy, and radiotherapy; these either remove or directly attack... (Review)
Review
Until now, three types of well-recognized cancer treatments have been developed, i.e., surgery, chemotherapy, and radiotherapy; these either remove or directly attack the cancer cells. These treatments can cure cancer at earlier stages but are frequently ineffective for treating cancer in the advanced or recurrent stages. Basic and clinical research on the tumor microenvironment, which consists of cancerous, stromal, and immune cells, demonstrates the critical role of antitumor immunity in cancer development and progression. Cancer immunotherapies have been proposed as the fourth cancer treatment. In particular, clinical application of immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1 antibodies, in various cancer types represents a major breakthrough in cancer therapy. Nevertheless, accumulating data regarding immune checkpoint inhibitors demonstrate that these are not always effective but are instead only effective in limited cancer populations. Indeed, several issues remain to be solved to improve their clinical efficacy; these include low cancer cell antigenicity and poor infiltration and/or accumulation of immune cells in the cancer microenvironment. Therefore, to accelerate the further development of cancer immunotherapies, more studies are necessary. In this review, we will summarize the current status of cancer immunotherapies, especially cancer vaccines, and discuss the potential problems and solutions for the next breakthrough in cancer immunotherapy.
Topics: Animals; Biomarkers; Cancer Vaccines; Clinical Studies as Topic; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Immunotherapy; Neoplasms; Treatment Outcome; Tumor Escape
PubMed: 33282961
DOI: 10.1155/2020/5825401