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1.
Recent Results Cancer Res ; 214: 1-70, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473848

RESUMO

Exploiting the unique specificity of monoclonal antibodies has revolutionized the treatment and diagnosis of haematological and solid organ malignancies; bringing benefit to millions of patients over the past decades. Recent achievements include conjugating antibodies with toxic payloads resulting in superior efficacy and/or reduced toxicity, development of molecular imaging techniques targeting specific antigens for use as predictive and prognostic biomarkers, the development of novel bi- and tri-specific antibodies to enhance therapeutic benefit and abrogate resistance and the success of immunotherapy agents. In this chapter, we review an overview of antibody structure and function relevant to cancer therapy and provide an overview of pivotal clinical trials which have led to regulatory approval of monoclonal antibodies in cancer treatment. We further discuss resistance mechanisms and the unique side effects of each class of antibody and provide an overview of emerging therapeutic agents.


Assuntos
Anticorpos Monoclonais/farmacologia , Imunoterapia , Neoplasias/terapia , Ensaios Clínicos como Assunto , Humanos
2.
Recent Results Cancer Res ; 214: 129-151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473851

RESUMO

The adoptive cell transfer (ACT) of genetically engineered T cell receptor (TCR) T cells is one of the burgeoning fields of immunotherapy, with promising results in current clinical trials. Presently, clinicaltrials.gov has over 200 active trials involving adoptive cell therapy. The ACT of genetically engineered T cells not only allows the ability to select for TCRs with desired properties such as high-affinity receptors and tumor reactivity but to further enhance those receptors allowing for better targeting and killing of cancer cells in patients. Moreover, the addition of genetic material, including cytokines and cytokine receptors, can increase the survival and persistence of the T cell allowing for complete and sustained remission of cancer targets. The potential for improvement in adoptive cell therapy is limitless, with genetic modifications targeting to improve weaknesses of ACT and to thus enhance receptor affinity and functional avidity of the genetically engineered T cells.


Assuntos
Engenharia Genética , Imunoterapia , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T , Linfócitos T/citologia , Humanos
3.
Recent Results Cancer Res ; 214: 153-167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473852

RESUMO

After more than a century of efforts to establish cancer immunotherapy in clinical practice, the advent of checkpoint inhibition (CPI) therapy was a critical breakthrough toward this direction (Hodi et al. in Cell Rep 13(2):412-424, 2010; Wolchok et al. in N Engl J Med 369(2):122-133, 2013; Herbst et al. in Nature 515(7528):563-567, 2014; Tumeh et al. in Nature 515(7528):568-571, 2014). Further, CPIs shifted the focus from long studied shared tumor-associated antigens to mutated ones. As cancer is caused by mutations in somatic cells, the concept to utilize these correlates of 'foreignness' to enable recognition and lysis of the cancer cell by T cell immunity seems an obvious thing to do.


Assuntos
Vacinas Anticâncer , Epitopos/imunologia , Imunoterapia , Neoplasias/terapia , Antígenos de Neoplasias/imunologia , Humanos
4.
Recent Results Cancer Res ; 214: 169-187, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31473853

RESUMO

Treatment of patients with advanced metastatic melanoma has for decades been a story of very limited success. This dramatically changed when therapy with anti-PD-1 checkpoint blocking antibodies was approved in the USA and Europe in 2014 and 2015, respectively. The therapy exploits the capacity of CD8+ T cells to specifically kill tumor cells. Within the tumor microenvironment, CD8+ T cell activity is blocked by suppressive signals received via PD-1, an inhibitory co-receptor and so-called checkpoint of T cell activation. PD-1 binds to its ligand PD-L1 on melanoma cells which dampens the T cell's activity. Antibodies blocking inhibitory PD-1/PD-L1 interaction release T cells from suppression. Treatment of late-stage disease melanoma patients with antibodies targeting the PD-1/PD-L1 axis, termed immune checkpoint blocking therapy (ICBT), yields clinical frequently long-lasting responses in 30-40% of cases. Despite this remarkable breakthrough, still the majority of patients resists ICBT or develops resistance after initial therapy response. Administration of anti-PD-1 antibodies in combination with antibodies targeting CTLA-4, another inhibitory immune checkpoint increased clinical responses rate up to 50% but at costs of higher treatment-related toxicities. Thus, strong efforts are now directed toward the understanding of therapy resistance, the identification of biomarkers predicting therapy response, and the development of alternative PD-1-based combination treatment to improve patient outcomes.


Assuntos
Linfócitos T CD8-Positivos/citologia , Imunoterapia , Melanoma/terapia , Receptor de Morte Celular Programada 1 , Anticorpos Monoclonais , Antígeno B7-H1 , Europa (Continente) , Humanos , Microambiente Tumoral
5.
Adv Exp Med Biol ; 1164: 225-233, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576552

RESUMO

Immune checkpoint blockade (ICB) has proved successful in the immunotherapeutic treatment of various human cancers. Despite its success, most patients are still not cured while immunogenic cold cancers are still poorly responsive. There is a need for novel clinical interventions in immunotherapy, either alone or in conjunction with ICB. Here, we outline our recent discovery that the intracellular signaling kinase glycogen synthase kinase-3 (GSK-3) is a central regulator of PD-1 in T-cells. We demonstrate the application of small molecule inhibitor (SMI) approaches to down-regulate PD-1 in tumor immunotherapy. GSK-3 SMIs were found as effective as anti-PD-1 in the elimination of melanoma in mouse models. We propose the development of novel SMIs to target co-receptors for the future of immunotherapy.


Assuntos
Regulação Neoplásica da Expressão Gênica , Quinase 3 da Glicogênio Sintase , Imunoterapia , Melanoma , Animais , Modelos Animais de Doenças , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Humanos , Melanoma/terapia , Camundongos , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T/fisiologia
6.
Cancer Radiother ; 23(6-7): 496-499, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471251

RESUMO

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.


Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias/radioterapia , Radiocirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Terapia Combinada/métodos , Previsões , França , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
7.
Rev Med Suisse ; 15(660): 1512-1515, 2019 Aug 28.
Artigo em Francês | MEDLINE | ID: mdl-31496176

RESUMO

The emergence of immunotherapy has generated great enthusiasm in oncology improving the prognosis of pathologies such as melanoma, lung cancer, kidney cancer, bladder and head and neck cancers. This enthusiasm concerns also older patients in view of the good tolerance of immunotherapy in young people. However, advanced age is linked to changes in the immune system, called immunosenescence, which could have a negative impact on the efficacy and toxicity of immunotherapy treatment. Knowledge in terms of efficacy and tolerance is limited for geriatric patients, few being included in clinical studies. This article summarizes the experience of immunotherapy in large clinical trials. It appears that the immune checkpoint inhibitors are effective and well tolerated in the elderly.


Assuntos
Imunoterapia , Neoplasias , Fatores Etários , Humanos , Tolerância Imunológica , Imunossenescência , Oncologia/tendências , Neoplasias/terapia
8.
Cancer Treat Rev ; 79: 101887, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31491661

RESUMO

Small cell lung cancer (SCLC) was defined as a "recalcitrant cancer" because of its dismal prognosis and lack of outcome improvements in the last 30 years. Immunotherapy with checkpoint inhibitors revolutionized treatment in many cancer types and results from the IMpower133 study, a double-blind placebo-controlled phase III trial, showed overall survival benefit for atezolizumab when added to standard platinum-etoposide chemotherapy in first-line SCLC setting for the first time since years. Trials with other checkpoint inhibitors, e.g. pembrolizumab, durvalumab, nivolumab and ipilimumab, are ongoing in various settings, but, to date, there are no defined factors to identify patients who are more likely to benefit from such treatments. This review summarizes results of immunotherapy trials in SCLC for first-line, maintenance and further-line therapies for single-agents and combinations with checkpoint inhibitors. Predictive factors from these trials are reviewed in order to identify their clinical value, with particular emphasis on PD-L1 expression on both tumor cells and in stroma, especially in pembrolizumab-treated patients, and tumor mutational burden, for patients treated with the ipilimumab and nivolumab combination.


Assuntos
Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/terapia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
9.
Cancer Radiother ; 23(6-7): 708-715, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31477442

RESUMO

Stereotactic radiation therapy of brain metastases is a treatment recognized as effective, well tolerated, applicable for therapeutic indications codified and validated by national and international guidelines. However, the effectiveness of this irradiation, the evolution of patient care and the technical improvements enabling its implementation make it possible to consider it in more complex situations: proximity of brain metastases to organs at risk; large, cystic, haemorrhagic or multiple brain metastases, combination with targeted therapies and immunotherapy, stereotactic radiotherapy in patients with a pacemaker. This article aims to put forward the arguments available to date in the literature and those resulting from clinical practice to provide decision support for the radiation oncologists.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Órgãos em Risco , Radiocirurgia/métodos , Neoplasias Encefálicas/patologia , Tronco Encefálico , Hemorragia Cerebral/complicações , Terapia Combinada/métodos , Contraindicações de Procedimentos , Humanos , Imunoterapia , Imagem por Ressonância Magnética/efeitos adversos , Terapia de Alvo Molecular , Nervo Óptico , Marca-Passo Artificial , Carga Tumoral
10.
Ther Umsch ; 76(4): 187-194, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498037

RESUMO

Immunotherapies - Overview, mode of action and clinical implications Abstract. The introduction of immunotherapies has led to major advances in the treatment of cancer patients. The mainstays of immunotherapies in clinical routine are immune checkpoint inhibitors. Immune checkpoints like CTLA-4 or the PD-1 / PD-L1 axis are important contributors to the immune homeostasis by preventing overshooting immune responses against pathogens and thus preventing collateral damage to normal tissue, or by preventing autoimmunity. However, immune checkpoints can impede the development of an efficient anti-tumor immune response. Thus, therapeutic monoclonal antibodies against CTLA-4 and PD-1 or PD-L1 displayed remarkable clinical activity such as complete sustained clinical remission even in patients bearing multiple metastases. Malignant melanoma, non-small cell lung cancer or Hodgkin's lymphoma are examples of cancer entities with especially well clinical responses to immune checkpoint inhibitors. This fast-developing field is rapidly expanding the indications for immune checkpoint inhibitors and combinations with other therapeutic strategies like vessel-modulating agents or classical chemotherapy are in preclinical and clinical testing. In this article, the mechanistic principles of immune checkpoint inhibition and their clinical applications are illustrated.


Assuntos
Imunoterapia , Neoplasias/terapia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Humanos , Imunoterapia/métodos
11.
Ther Umsch ; 76(4): 195-198, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31498041

RESUMO

Immunotherapy - immune-related adverse events and their management Abstract. Checkpoint-Inhibition has become an important part of modern oncological treatment strategies for many patients with cancer. The development of this new class of anti-cancer drugs has begun for ten years and showed meanwhile a specific new side effect profile. Since the mode of action of checkpoint inhibitors is immune modulation the side effects are particularly different to so far established anti-cancer drugs. Because of the immunological nature of side effects, the spectrum is wide, and the symptoms are amble. Additionally, the side effects can appear at very different time points after the administration of the checkpoint inhibitor. Therefore, the recognition and the management are a new challenge for the care teams. Only if the whole care team is able to understand, diagnose and efficiently manage the side effects the therapeutic potential of this new class of anti-cancer drugs can be made useful for the patients. The article aims to provide information for the care teams to recognize and manage side effects of checkpoint-inhibitors.


Assuntos
Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/terapia , Humanos , Fatores Imunológicos , Oncologia , Síndromes Neurotóxicas/etiologia
12.
Medicine (Baltimore) ; 98(36): e16873, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490371

RESUMO

At present, intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is recommended for prophylaxis purposes after transurethral resection of bladder tumor, but has chances of recurrence. Radical cystectomy reduces the risk of recurrence in bladder cancer patients, but may have chances of postoperative complications. The objective of the study was to test the hypothesis that radical cystectomy has overtreatment and definitive BCG immunotherapy has undertreatment in intermediate or high-risk nonmuscle invasive bladder cancer patients. Data regarding biopsies, ultrasound, the computed tomography scan, adopted treatment strategy, treatment-emergent adverse effect, and a follow-up period of 312 patients with confirmed nonmuscle invasive bladder cancer (pTa, pTis, or pT1 stage; intermediate or high-risk cancer) were reviewed. Patients who had received definitive intravesical BCG immunotherapy were included in BCG group (n = 210) and those who underwent radical cystectomy were included in RXC group (n = 87). Clinical decision-making for treatment strategies was evaluated for both groups. Cystitis was frequently observed in all patients who received BCG immunotherapy. In RXC group, ileus was frequently observed in all patients in early days after the operation. During 2 years of the follow-up period, biopsies, ultrasound, and the computed tomography scan reported that BCG group had fewer numbers of negative cancer patients after treatment than the RXC group after surgery (P < .0001). Total expenditure for BCG immunotherapy was higher than radical cystectomy (22,945 ±â€Š945 ¥/patient vs 17,985 ±â€Š545 ¥/patient; P < .0001). Definitive BCG immunotherapy had undertreatment and radical cystectomy had overtreatment for intermediate or high-risk invasive bladder cancer patients (level of evidence III).


Assuntos
Vacina BCG/uso terapêutico , Cistectomia/estatística & dados numéricos , Imunoterapia/métodos , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Adolescente , Adulto , Idoso , Vacina BCG/efeitos adversos , Vacina BCG/economia , Análise Custo-Benefício , Cistectomia/efeitos adversos , Cistectomia/economia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Imunoterapia/economia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores Socioeconômicos , Neoplasias da Bexiga Urinária/patologia , Adulto Jovem
13.
Magy Onkol ; 63(3): 239-245, 2019 09 18.
Artigo em Húngaro | MEDLINE | ID: mdl-31538441

RESUMO

Skin cancers represent the most common type of malignancy. The incidence rate of melanoma and non-melanoma skin cancer depicts a continuous rise worldwide, which is attributed mainly (but not exclusively) to the growing incidence of non-melanoma skin cancer in the elderly population. Most skin cancer types are sensitive to immunotherapy. Melanoma, Merkel cell carcinoma, cutaneous squamous cell carcinoma showed response rates of at least 40% for PD-1 inhibitor therapy as reported in recent articles. In this article we review the current and future immunotherapy agents and procedures for skin cancers.


Assuntos
Imunoterapia/mortalidade , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Carcinoma de Célula de Merkel/imunologia , Carcinoma de Célula de Merkel/patologia , Carcinoma de Célula de Merkel/terapia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Intervalo Livre de Doença , Feminino , Humanos , Hungria , Masculino , Melanoma/imunologia , Melanoma/patologia , Melanoma/terapia , Terapia de Alvo Molecular/métodos , Prognóstico , Medição de Risco , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida , Resultado do Tratamento
14.
Gan To Kagaku Ryoho ; 46(9): 1361-1366, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530771

RESUMO

This year, the genetic testing for cancer genome medicine approved in Japan, and the clinical basis for this medical area is developed. Focus will likely fall not only on genetic analysis in tissues, but also on genomic analysis by liquid biopsy using patient body fluids such as blood, saliva and urine. The advantages of liquid biopsy are the fact that it is minimally invasive and the possibility of broadening the diagnosis and selection of therapeutic agents, even in cases in which it is difficult to collect tumor tissues. Liquid biopsies of cancer patients will enable, circulating tumor cell(CTC), cell free DNA(cfDNA), circulating tumor cell DNA(ctDNA), exosomes and microRNA(miRNA). The potential usefulness of liquid biopsy for cancer diagnosis, recurrence prediction and monitoring of treatment effect has been mentioned in various manuscripts. In immunotherapy, liquid genetic biomarkers for predicting the therapeutic effect of immune checkpoint inhibitors are under development worldwide. Although issues such as standardization of the measurement methods and the samples used remain, early diagnosis of cancer by liquid biopsy may become a reality in the near future.


Assuntos
Genômica , Biomarcadores Tumorais , Humanos , Imunoterapia , Japão , Biópsia Líquida , Recidiva Local de Neoplasia
15.
Gan To Kagaku Ryoho ; 46(9): 1367-1371, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530772

RESUMO

Recent advances in cancer immunotherapies, such as immune checkpoint inhibitors(ICIs), have shown some durable clinical responses in patients with various types of advanced cancers. The development of the next-generation sequencing technologies can result in a comprehensive characterization of the human cancer genomes. Personalized immunotherapy and precision cancer medicine might enable the next generation of rational cancer immunotherapy. Conventional cancer vaccines are designed to target tumor-associated antigens(TAAs), which are overexpressed in cancers. However, since TAAs are also expressed in normal tissues, cancer vaccine against TAAs can potentially initiate central and peripheral tolerance responses, which results in low vaccination efficiency. Cancer neoantigens derived from somatic mutations in tumor tissue represent highly immunogenic and can escape from central thymic tolerance. They are suggested to provide tumor specific targets for personalized cancer vaccines. Therefore, neoantigen-based cancer vaccine, which can induce tumor-specific cytotoxic T lymphocytes( CTLs), should be developed. The efficacy of current immunotherapies also remains limited due to the immunosuppressive tumor microenvironment, which leads to CTLs exhaustion or anergy and the escape of tumor cells from immune attack. The combination of neoantigen-based cancer vaccine and ICIs should be a potential therapeutic approach. In this paper, we provide a brief overview of the recent advances in the development of neoantigen-based cancer vaccines.


Assuntos
Vacinas Anticâncer , Neoplasias , Antígenos de Neoplasias , Humanos , Imunoterapia , Medicina de Precisão , Microambiente Tumoral
16.
Gan To Kagaku Ryoho ; 46(9): 1372-1376, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530773

RESUMO

T cells are critical effector immune cells, and mutation-derived neoantigens are critical tumor-specific antigens in natural immune responses to cancer(cancer immunosurveillance). However, the underlying mechanisms are poorly understood, particularly in the human clinical setting, such as how many tumor antigens are related to cancer elimination and whether immunodominance of antigens exist in humans. Furthermore, it is unclear whether specific T cells recognizing neoantigens can control cancer for a long time in an equilibrium state. Cancer immunotherapy including immune checkpoint inhibitors (ICIs)such as PD-1 and CTLA-4 blockades has attracted much attention for cancer treatment, but they remain effective only in a minority of patients. However, the efficacy of ICIs, which is characterized by long term durable responses has suggested that host immunity, if re-activated, can eliminate cancer cells or maintain cancer for a long time(therapeutically induced cancer immune elimination or equilibrium). Recent reports show that the loss of neoantigens has occurred at the DNA and RNA level as results of both naturally and therapeutically induced tumor-specific immune responses, leading to tumor immune escape(re-escape). Here we focus on the role of neoantigens in naturally and therapeutically induced immunoediting revealed by cancer immunogenomics approaches utilizing clinical samples to develop effective neoantigen-based cancer immunotherapies.


Assuntos
Neoplasias , Antígenos de Neoplasias , Humanos , Imunoterapia , Mutação , Linfócitos T
17.
Adv Exp Med Biol ; 1152: 131-172, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456183

RESUMO

Metastatic breast cancer is the most common cancer in women after skin cancer, with a 5-year survival rate of 26%. Due to its high prevalence, it is important to develop therapies that go beyond those that just provide palliation of symptoms. Currently, there are several types of therapies available to help treat breast cancer including: hormone therapy, immunotherapy, and chemotherapy, with each one depending on both the location of metastases and morphological characteristics. Although technological and scientific advancements continue to pave the way for improved therapies that adopt a targeted and personalized approach, the fact remains that the outcomes of current first-line therapies have not significantly improved over the last decade. In this chapter, we review the current understanding of the pathology of metastatic breast cancer before thoroughly discussing local and systemic therapies that are administered to patients diagnosed with metastatic breast cancer. In addition, our review will also elaborate on the genetic profile that is characteristic of breast cancer as well as the local tumor microenvironment that shapes and promotes tumor growth and cancer progression. Lastly, we will present promising novel therapies being developed for the treatment of this disease.


Assuntos
Neoplasias da Mama/terapia , Metástase Neoplásica/terapia , Antineoplásicos/uso terapêutico , Feminino , Humanos , Imunoterapia , Microambiente Tumoral
18.
Anticancer Res ; 39(8): 4517-4523, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366554

RESUMO

BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) have dramatically changed the clinical outcomes of advanced tumours. However, biomarkers for monitoring immunological features during immunotherapy remain unclear, especially those in the peripheral blood, which are easily available. This study evaluated the usefulness of nCounter Analysis System in identifying immunological biomarkers in peripheral blood mononuclear cells (PBMCs) during ICI therapy. PATIENTS AND METHODS: PBMCs from two patients who responded well to ICI therapy were used, and the expression levels of immune-related mRNA and extracellular proteins were analyzed. RESULTS: Changes in the expression levels of 55 genes from pre-treatment to on-treatment were bioinformatically similar between the two cases. The expression levels of PD-1 were consistent with those by flow cytometry analysis, a reliable tool for monitoring various markers. CONCLUSION: The nCounter Analysis System may be a potent tool to simultaneously investigate genes and proteins on PBMCs as biomarkers during immunotherapy using a small amount of sample.


Assuntos
Biomarcadores Tumorais/sangue , Imunoterapia , Neoplasias Pulmonares/sangue , Proteínas de Neoplasias/genética , Idoso , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue
19.
Anticancer Res ; 39(8): 4525-4532, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366555

RESUMO

BACKGROUND/AIM: In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy using T lymphocytes activated in vitro with or without dendritic cells vaccination (DCs), in combination with 1st-line chemotherapies in terms of the survival of patients with advanced colorectal cancer (CRC). PATIENTS AND METHODS: A total of 198 patients who were diagnosed with advanced CRC and administered 1st-line chemotherapies were enrolled in this study. The correlation between overall survival (OS) and various clinical factors was examined by univariate and multivariate analyses. RESULTS: Univariate analyses revealed that the prognosis was improved in CRC patients who received immune-cell therapy with PS 0, bevacizumab (BV), and capecitabine-including regimens (Cap). Finally, multivariate analysis demonstrated that PS=0, and the combination of immune-cell therapy and Cap provided a survival benefit in patients with advanced CRC. CONCLUSION: The survival benefit could be potentially obtained with better PS by the combination of immune-cell therapy and Cap as a 1st-line setting in patients with CRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Imunoterapia , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Terapia Baseada em Transplante de Células e Tecidos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Terapia Combinada , Desoxicitidina/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade
20.
Anticancer Res ; 39(8): 4533-4537, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366556

RESUMO

BACKGROUND/AIM: Serum-derived macrophage activating factor, serum-MAF, is known to increase the phagocytic activity of macrophages by enhancing the engulfment efficiency. To elucidate the mechanisms underlying phagocytic activation, morphological changes were observed and analyzed. MATERIALS AND METHODS: Morphological changes in macrophages were observed and quantitatively analyzed using scanning electron microscope (SEM) and confocal microscope. RESULTS: SEM and confocal microscopy images revealed frill-like structures and active actin accumulations, respectively, in serum-MAF treated macrophages. Actin accumulation was induced within 5 min following serum-MAF treatment. CONCLUSION: Serum-MAF induced a rapid rearrangement of cytoskeletal actin and enhanced phagocytic activity. Findings of the current study may contribute to the development of techniques that facilitate activation of the human immune system, which in turn may be beneficial for cancer immunotherapy.


Assuntos
Actinas/química , Macrófagos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-maf/farmacologia , Actinas/ultraestrutura , Humanos , Imunoterapia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Microscopia Confocal , Microscopia Eletrônica de Varredura , Proteínas Proto-Oncogênicas c-maf/genética , Células U937 , Proteína de Ligação a Vitamina D/química , Proteína de Ligação a Vitamina D/metabolismo
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