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1.
J Med Case Rep ; 15(1): 332, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34215343

RESUMO

BACKGROUND: Immunotherapy has become an efficacious option in the management of solid organ malignancies. Immune-related adverse events including pneumonitis are well described and may be particularly of concern in patients receiving immunotherapy for non-small-cell lung cancer. CASE PRESENTATIONS: In this paper, we describe three cases of immunotherapy-induced pneumonitis occurring in the management of lung malignancy. Our cases include a 54-year-old Caucasian woman with squamous cell lung cancer who was successfully rechallenged with immunotherapy after prior significant pneumonitis, a 65-year-old Caucasian man with metastatic squamous cell lung cancer who developed pneumonitis after multiple cycles of uneventful immunotherapy, and a 73-year-old Caucasian man with squamous cell lung cancer who developed early-onset pneumonitis with rebound on steroid taper. CONCLUSIONS: This case series has provided further insight into the presentation and risk factors for pneumonitis in patients with non-small-cell lung cancer. Each of the cases of immunotherapy-induced pneumonitis illustrates the different potential patterns that may arise when immunotherapy-induced pneumonitis develops. This case series provides key learning points that may assist physicians managing non-small-cell lung cancer with immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Pneumonia , Idoso , Feminino , Humanos , Imunoterapia , Masculino , Pessoa de Meia-Idade
2.
Acta Gastroenterol Belg ; 84(2): 371-374, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34217191

RESUMO

Hepatocellular carcinoma accounts for 90% of primary liver cancers and represents a growing health problem worldwide. We report the complex case of a 71 year-old patient diagnosed with a large hepatocellular carcinoma and presenting an extensive vascular invasion of the middle hepatic vein and the inferior caval vein ascending to the right atrium with no extrahepatic spread. Due to several comorbidities, a systemic treatment by tyrosine kinase inhibitors was contraindicated. After discussion at the multidisciplinary hepatology tumor board, he was referred for selective internal radiation therapy. Unfortunately, the work-up showed an important lung shunt not allowing radioembolization. No clear recommendations are available in this situation. The decision was made to propose a combination treatment by transarterial chemoembolization, that was performed using a new generation of radio-opaque microspheres loaded with doxorubicin, followed by immunotherapy. This allowed a complete response with a very good quality of life.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/terapia , Humanos , Imunoterapia , Neoplasias Hepáticas/terapia , Masculino , Qualidade de Vida , Resultado do Tratamento
3.
BMJ Case Rep ; 14(7)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230042

RESUMO

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease frequently associated with ovarian teratomas. In cases where an ovarian teratoma is identified, treatment involves prompt removal of the ovarian teratoma, resulting in significant clinical improvement and decreased incidence of relapse. We present the case of a 14-year-old female patient admitted for progressively worsening psychiatric and neurological status, diagnosed with anti-NMDAR encephalitis, and negative initial imaging for ovarian pathology. She was in the hospital for 8 months requiring admission to the intensive care unit and multiple courses of immunotherapy before clinical improvement. Three months after discharge, she was readmitted with clinical relapse and repeat imaging showed an ovarian teratoma. Removal of the teratoma resulted in sustained clinical improvement with return to baseline and no further relapse. Our case report highlights the importance of maintaining a high suspicion for an underlying ovarian teratoma in a female patient with anti-NMDAR encephalitis, even when initial imaging is negative. Currently, there are limited data on recommendations for repeat imaging. Therefore, we recommend repeat imaging in patients resistant to multiple lines of treatment or presenting with clinical relapse.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Neoplasias Ovarianas , Teratoma , Adolescente , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/terapia , Feminino , Humanos , Imunoterapia , Recidiva Local de Neoplasia , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/diagnóstico por imagem , Receptores de N-Metil-D-Aspartato , Teratoma/complicações , Teratoma/diagnóstico por imagem , Teratoma/cirurgia
4.
Anticancer Res ; 41(7): 3419-3427, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230137

RESUMO

BACKGROUND/AIM: Liver metastases are among the principal mortality causes in cancer patients. Dendritic cell immunotherapies have shown promising results in some tumors by mediating immunological mechanisms that could be involved in liver metastases during primary tumor growth. The present study aimed to evaluate the impact of prophylactic dendritic cell vaccination on the liver of mice with 4T1 mouse breast carcinoma. MATERIALS AND METHODS: Adult female Balb/c mice were submitted or not to vaccination with dendritic cells before the induction of 4T1 tumor lineage. Liver tissues from mice were analyzed by flow cytometry (markers CD3, CD4, CD8, CD25, IL-10, IL-12, IL-17, TNF-α, IFN-γ, T-bet, GATA3, RORγt, and FoxP3) and hematoxylin-eosin. The dendritic cell vaccine was differentiated and matured ex vivo from the bone marrow. RESULTS: Prophylactic vaccination reduced areas of liver metastases (p=0.0049), induced an increase in the percentage of total T and cytotoxic T lymphocytes (p<0.0001), as well as FoxP3+ (p<0.0001). It also increased the levels of cytokines IL-10 and IL-17 in helper T lymphocytes (p<0.0001). CONCLUSION: The prophylactic dendritic cell vaccine changed the cell phenotype in the immune response of liver, and it was able to reduce metastases. Cytotoxic T cells and regulatory T lymphocytes were more present, likewise, the production of IL-10 and IL-7 simultaneously, demonstrating that the vaccine can induce a state of control of pro-inflammatory responses, which can provide a less favorable environment for metastatic tumor growth.


Assuntos
Neoplasias da Mama/imunologia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Neoplasias Hepáticas/imunologia , Fígado/imunologia , Animais , Biomarcadores Tumorais/imunologia , Medula Óssea/imunologia , Neoplasias da Mama/patologia , Modelos Animais de Doenças , Feminino , Imunidade/imunologia , Imunoterapia/métodos , Fígado/patologia , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Vacinação/métodos
5.
Anticancer Res ; 41(7): 3673-3682, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230166

RESUMO

AIM: This study aimed to investigate useful prognostic factors of immunotherapy in patients with lung cancer. PATIENTS AND METHODS: We retrospectively observed 73 patients who underwent immunotherapy (nivolumab, pembrolizumab, and atezolizumab) for lung cancer. The systemic inflammatory score (SIS) was calculated as the sum of the following factors scored one point each: Hemoglobin <12.5 g/dl and serum albumin <3.6 g/dl, resulting in scores of 0-2. We examined the correlation between the SIS and initial tumor response and progression-free and overall survival with other existing markers, namely tumor programmed death-ligand 1 (PD-L1) expression level; neutrophil-to-lymphocyte ratio (NLR); modified Glasgow prognostic score; and prognostic nutritional index, etc. Results: SIS ≤1 was significantly associated with better initial tumor response. In multivariate analysis, PD-L1 expression ≥50% (p=0.010), SIS ≤1 (p=0.028) and NLR <5.6 (p=0.047) were significantly associated with longer progression-free survival, and SIS ≤1 (p=0.030) and NLR <5.6 (p=0.037) were associated with longer overall survival. CONCLUSION: SIS is a useful marker of the efficacy of immunotherapy that can be obtained via routine blood tests.


Assuntos
Inflamação/patologia , Neoplasias Pulmonares/patologia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imunoterapia/métodos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Nivolumabe/uso terapêutico , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
6.
Molecules ; 26(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207756

RESUMO

Since December 2019, humanity has faced an important global threat. Many studies have been published on the origin, structure, and mechanism of action of the SARS-CoV-2 virus and the treatment of its disease. The priority of scientists all over the world has been to direct their time to research this subject. In this review, we highlight chemical studies and therapeutic approaches to overcome COVID-19 with seven different sections. These sections are the structure and mechanism of action of SARS-CoV-2, immunotherapy and vaccine, computer-aided drug design, repurposing therapeutics for COVID-19, synthesis of new molecular structures against COVID-19, food safety/security and functional food components, and potential natural products against COVID-19. In this work, we aimed to screen all the newly synthesized compounds, repurposing chemicals covering antiviral, anti-inflammatory, antibacterial, antiparasitic, anticancer, antipsychotic, and antihistamine compounds against COVID-19. We also highlight computer-aided approaches to develop an anti-COVID-19 molecule. We explain that some phytochemicals and dietary supplements have been identified as antiviral bioproducts, which have almost been successfully tested against COVID-19. In addition, we present immunotherapy types, targets, immunotherapy and inflammation/mutations of the virus, immune response, and vaccine issues.


Assuntos
COVID-19/prevenção & controle , Antivirais/química , Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , COVID-19/patologia , COVID-19/terapia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Síndrome da Liberação de Citocina/prevenção & controle , Desenho de Fármacos , Reposicionamento de Medicamentos , Humanos , Imunoterapia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia
7.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207286

RESUMO

Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget's "Seed and Soil" hypothesis, metastatic capacity is determined not only by the internal oncogenic driving force but also by the external environment of tumor cells. Throughout the body, macrophages are required for maintaining tissue homeostasis, even in the tumor milieu. To fulfill these multiple functions, macrophages are polarized from the inflammation status (M1-like) to anti-inflammation status (M2-like) to maintain the balance between inflammation and regeneration. However, tumor cell-enforced tumor-associated macrophages (TAMs) (a high M2/M1 ratio status) are associated with poor prognosis for most solid tumors, such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up to 50% of the tumor mass, exert both protumor and immunosuppressive effects in promoting tumor metastasis through secretion of interleukin 10 (IL10), transforming growth factor ß (TGFß), and VEGF, expression of PD-1 and consumption of arginine to inhibit T cell anti-tumor function. However, the underlying molecular mechanisms by which the tumor microenvironment favors reprogramming of macrophages to TAMs to establish a premetastatic niche remain controversial. In this review, we examine the latest investigations of TAMs during tumor development, the microenvironmental factors involved in macrophage polarization, and the mechanisms of TAM-mediated tumor metastasis. We hope to dissect the critical roles of TAMs in tumor metastasis, and the potential applications of TAM-targeted therapeutic strategies in cancer treatment are discussed.


Assuntos
Neoplasias/patologia , Microambiente Tumoral , Macrófagos Associados a Tumor/imunologia , Animais , Diferenciação Celular , Humanos , Imunoterapia/métodos , Metástase Neoplásica , Neoplasias/imunologia , Neoplasias/terapia , Macrófagos Associados a Tumor/patologia
8.
Molecules ; 26(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: covidwho-1264498

RESUMO

Since December 2019, humanity has faced an important global threat. Many studies have been published on the origin, structure, and mechanism of action of the SARS-CoV-2 virus and the treatment of its disease. The priority of scientists all over the world has been to direct their time to research this subject. In this review, we highlight chemical studies and therapeutic approaches to overcome COVID-19 with seven different sections. These sections are the structure and mechanism of action of SARS-CoV-2, immunotherapy and vaccine, computer-aided drug design, repurposing therapeutics for COVID-19, synthesis of new molecular structures against COVID-19, food safety/security and functional food components, and potential natural products against COVID-19. In this work, we aimed to screen all the newly synthesized compounds, repurposing chemicals covering antiviral, anti-inflammatory, antibacterial, antiparasitic, anticancer, antipsychotic, and antihistamine compounds against COVID-19. We also highlight computer-aided approaches to develop an anti-COVID-19 molecule. We explain that some phytochemicals and dietary supplements have been identified as antiviral bioproducts, which have almost been successfully tested against COVID-19. In addition, we present immunotherapy types, targets, immunotherapy and inflammation/mutations of the virus, immune response, and vaccine issues.


Assuntos
COVID-19/prevenção & controle , Antivirais/química , Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , COVID-19/patologia , COVID-19/terapia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Síndrome da Liberação de Citocina/prevenção & controle , Desenho de Fármacos , Reposicionamento de Medicamentos , Humanos , Imunoterapia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/fisiologia
9.
J Med Case Rep ; 15(1): 336, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34225811

RESUMO

BACKGROUND: Nivolumab, an anti-programmed cell death protein 1 antibody, is commonly used as an immune checkpoint inhibitor in various cancers. Various adverse events are associated with these therapies, including hepatitis, dermatitis, and myocarditis. Myocarditis is a relatively rare but potentially fatal immune-mediated adverse reaction. CASE PRESENTATION: We report a case of colon cancer in a 56-year-old Chinese patient with lung and liver metastasis who developed fulminant myocarditis by nivolumab and survived with the support of extracorporeal membrane oxygenation. After six cycles (within 3 months) of nivolumab treatment, the patient developed chest tightness and was hospitalized. A diagnosis of fulminant myocarditis associated with immunotherapy was confirmed based on the clinical manifestations and laboratory examinations. He recovered well and was discharged on day 45 after management with extracorporeal membrane oxygenation, intravenous methylprednisolone, and immunoglobulin. CONCLUSIONS: This case illustrates a severe cardiovascular complication of immunotherapy, strongly suggesting the necessity of close monitoring for outpatient usage of nivolumab. Additionally, our experience provided an efficient management strategy of extracorporeal membrane oxygenation in terms of life-threatening conditions.


Assuntos
Oxigenação por Membrana Extracorpórea , Miocardite , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Masculino , Pessoa de Meia-Idade , Miocardite/induzido quimicamente , Nivolumabe/efeitos adversos
10.
Acta Biomed ; 92(3): e2021033, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34212930

RESUMO

We report the case of a 15-year-old boy who developed eosinophilic esophagitis (EoE) during cow's milk oral immunotherapy (CM-OIT). In order to not completely invalidate OIT benefits, baked milk-containing foods were allowed instead of a strict CM-free diet. However, histological remission of EoE was reached only after a strict cow's milk-free diet, not associated to pharmacological treatment. Nevertheless, given the limited data on real incidence of food OIT related EoE and potential beneficial treatment for this condition, we highlight the need of prospective studies aimed to evaluate if a strict CM free diet in OIT related EoE is always necessary to obtain remission of the disease or similarly to CM EoE, baked milk-containing foods" diet could be abeneficial treatment also in these patients.


Assuntos
Esofagite Eosinofílica , Hipersensibilidade a Leite , Adolescente , Animais , Bovinos , Dieta , Esofagite Eosinofílica/etiologia , Esofagite Eosinofílica/terapia , Feminino , Humanos , Imunoterapia/efeitos adversos , Masculino , Leite , Hipersensibilidade a Leite/terapia , Estudos Prospectivos
11.
Tumour Biol ; 43(1): 115-127, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34219680

RESUMO

BACKGROUND: The widespread introduction of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) has led to durable responses but still many patients fail and are treated beyond progression. OBJECTIVE: This study investigated whether readily available blood-based tumor biomarkers allow accurate detection of early non-responsiveness, allowing a timely switch of therapy and cost reduction. METHODS: In a prospective, observational study in patients with NSCLC treated with nivolumab or pembrolizumab, five serum tumor markers were measured at baseline and every other week. Six months disease control as determined by RECIST was used as a measure of clinical response. Patients with a disease control <  6 months were deemed non-responsive. For every separate tumor marker a criterion for predicting of non-response was developed. Each marker test was defined as positive (predictive of non-response) if the value of that tumor marker increased at least 50% from the value at baseline and above a marker dependent minimum value to be determined. Also, tests based on combination of multiple markers were designed. Specificity and sensitivity for predicting non-response was calculated and results were validated in an independent cohort. The target specificity of the test for detecting non-response was set at >  95%, in order to allow its safe use for treatment decisions. RESULTS: A total of 376 patients (training cohort: 180, validation cohort: 196) were included in our analysis. Results for the specificity of the single marker tests in the validation set were CEA: 98·3% (95% CI: 90·9-100%), NSE: 96·5% (95% CI: 87·9-99·6%), SCC: 96·5% (95% CI: 88·1-99·6%), Cyfra21·1 : 91.8% (95% CI: 81·9-97·3%), and CA125 : 86·0% (95% CI: 74·2-93·7%). A test based on the combination of Cyfra21.1, CEA and NSE accurately predicted non-response in 32.3% (95% CI 22.6-43.1%) of patients 6 weeks after start of immunotherapy. Survival analysis showed a significant difference between predicted responders (Median PFS: 237 days (95% CI 184-289 days)) and non-responders (Median PFS: 58 days (95% CI 46-70 days)) (p <  0.001). CONCLUSIONS: Serum tumor marker based tests can be used for accurate detection of non-response in NSCLC, thereby allowing early and safe discontinuation of immunotherapy in a significant subset of patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Imunoterapia/mortalidade , Neoplasias Pulmonares/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Técnicas de Apoio para a Decisão , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
12.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 475-480, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238426

RESUMO

Breast cancer has become the most common cancer for women in China.Lack of effective therapeutic targets,triple negative breast cancer(TNBC)has poorer prognosis compared with other subtypes of breast cancer.Tumor infiltrating lymphocytes(TILs)are a group of heterogeneous lymphocytes around the tumor,which are believed as immunoreactive products of host immune response to tumor antigens.At present,there have been reports on the predictive effect of TILs on the prognosis of breast cancer,and the available studies focus mainly on TNBC.This article briefly reviews the recent progress of tumor infiltrating lymphocytes in immunotherapy of TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais , China , Feminino , Humanos , Imunoterapia , Linfócitos do Interstício Tumoral , Prognóstico , Neoplasias de Mama Triplo Negativas/terapia
13.
World J Gastroenterol ; 27(24): 3483-3501, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239264

RESUMO

Pancreatic cancer remains one of medicine's largest areas of unmet need. With five-year survival rates of < 8%, little improvement has been made in the last 50 years. Typically presenting with advance stage disease, treatment options are limited. To date, surgery remains the only potentially curative option, however, with such late disease presentation, the majority of patients are unresectable. Thus, new therapeutic options and a greater understanding of the complex stromal interactions within the tumour microenvironment are sorely needed to revise the dismal outlook for pancreatic cancer patients. Natural killer (NK) cells are crucial effector units in cancer immunosurveillance. Often used as a prognostic biomarker in a range of malignancies, NK cells have received much attention as an attractive target for immunotherapies, both as cell therapy and as a pharmaceutical target. Despite this interest, the role of NK cells in pancreatic cancer remains poorly defined. Nevertheless, increasing evidence of the importance of NK cells in this dismal prognosis disease is beginning to come to light. Here, we review the role of NK cells in pancreatic cancer, examine the complex interactions of these crucial effector units within pancreatic cancer stroma and shed light on the increasingly attractive use of NK cells as therapy.


Assuntos
Neoplasias Pancreáticas , Humanos , Imunoterapia , Células Matadoras Naturais , Neoplasias Pancreáticas/terapia , Prognóstico , Microambiente Tumoral
14.
Molecules ; 26(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205347

RESUMO

PURPOSE: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. EXPERIMENTAL DESIGN: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. RESULTS: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. CONCLUSIONS: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.


Assuntos
Receptor de Morte Celular Programada 1/agonistas , Receptores OX40/agonistas , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/terapia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunidade/efeitos dos fármacos , Imunoterapia/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fotoquimioterapia/métodos , Linfócitos T/efeitos dos fármacos , Neoplasias Urológicas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
15.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205019

RESUMO

Clinically, different approaches are adopted worldwide for the treatment of cancer, which still ranks second among all causes of death. Immunotherapy for cancer treatment has been the focus of attention in recent years, aiming for an eventual antitumoral effect through the immune system response to cancer cells both prophylactically and therapeutically. The application of nanoparticulate delivery systems for cancer immunotherapy, which is defined as the use of immune system features in cancer treatment, is currently the focus of research. Nanomedicines and nanoparticulate macromolecule delivery for cancer therapy is believed to facilitate selective cytotoxicity based on passive or active targeting to tumors resulting in improved therapeutic efficacy and reduced side effects. Today, with more than 55 different nanomedicines in the market, it is possible to provide more effective cancer diagnosis and treatment by using nanotechnology. Cancer immunotherapy uses the body's immune system to respond to cancer cells; however, this may lead to increased immune response and immunogenicity. Selectivity and targeting to cancer cells and tumors may lead the way to safer immunotherapy and nanotechnology-based delivery approaches that can help achieve the desired success in cancer treatment.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Sistema Imunitário/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Antineoplásicos Imunológicos/química , Antineoplásicos Imunológicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Humanos , Imunoterapia , Nanopartículas , Neoplasias/imunologia
16.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208111

RESUMO

Anti-PD1/PD-L1 immunotherapy has emerged as a standard of care for stage III-IV non-small cell lung cancer (NSCLC) over the past decade. Patient selection is usually based on PD-L1 expression by tumor cells and/or tumor mutational burden. However, mutations in oncogenic drivers such as EGFR, ALK, BRAF, or MET modify the immune tumor microenvironment and may promote anti-PD1/PD-L1 resistance. In this review, we discuss the molecular mechanisms associated with these mutations, which shape the immune tumor microenvironment and may impede anti-PD1/PD-L1 efficacy. We provide an overview of the current clinical data on anti-PD1/PD-L1 efficacy in NSCLC with oncogenic driver mutation.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Mutação/genética , Oncogenes/genética , Animais , Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/genética
17.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208157

RESUMO

Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. Understanding the role of brain-specific tumor immune microenvironment (TIME) is important for developing rationale-driven ICI-based combination strategies that circumvent tumor intrinsic and extrinsic factors and complex positive feedback loops associated with resistance to ICIs in RCC-BM via combination with ICIs involving other immunological pathways, anti-antiangiogenic multiple tyrosine kinase inhibitors, and radiotherapy; therefore, novel combination approaches are being developed for synergistic potential against RCC-BM; however, further prospective investigations with longer follow-up periods are required to improve the efficacy and safety of combination treatments and to elucidate dynamic predictive biomarkers depending on the interactions in the brain TIME.


Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Carcinoma de Células Renais/patologia , Imunoterapia , Neoplasias Renais/patologia , Humanos , Imunossupressão , Microambiente Tumoral
18.
Anticancer Res ; 41(7): 3247-3252, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230118

RESUMO

Cancer immunotherapy is an evolving field of research. Cytokines have been conceptualized as an anticancer therapy for longer than most other cancer immunotherapy modalities. Yet, to date, only two cytokines are FDA-approved: IFN-α and IL-2. Despite the initial breakthrough, both agents have been superseded by other, more efficacious agents such as immune checkpoint inhibitors. Several issues persist with cytokine-based cancer therapies; these are broadly categorised into a) high toxicity and b) low efficacy. Despite the only moderate benefits with early cytokine-based cancer therapies, advances in molecular engineering, genomics, and molecular analysis hold promise to optimise and reinstate cytokine-based therapies in future clinical practice. This review considers five important concepts for the successful clinical application of cytokine-based cancer therapies including: (i) improving pharmacokinetics and pharmacodynamics, (ii) improving local administration strategies, (iii) understanding context-dependent interactions in the tumour-microenvironment, (iv) elucidating the role of genetic polymorphisms, and (v) optimising combination therapies. IL-10 has been the focus of attention in recent years and is discussed herein as an example.


Assuntos
Citocinas/farmacologia , Citocinas/uso terapêutico , Interleucina-10/farmacologia , Interleucina-10/uso terapêutico , Neoplasias/imunologia , Neoplasias/terapia , Animais , Humanos , Imunoterapia/métodos , Polimorfismo Genético/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
19.
Anticancer Res ; 41(7): 3371-3387, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230133

RESUMO

BACKGROUND/AIM: We compared the therapeutic efficacy of two recently developed experimental anticancer technologies: 1) in situ vaccination based on local immunotherapy with CpG oligonucleotides and anti-OX40 antibodies to activate antitumor immune response and 2) "Karanahan" technology [from the Sanskrit karana ('source') + han ('to kill')] based on the combined injection of cyclophosphamide and double-stranded DNA to eradicate cancer stem cells. MATERIALS AND METHODS: The anticancer approaches were compared on three types of mouse malignant tumors with different grades of immunogenicity: weakly immunogenic carcinoma Krebs-2, moderately immunogenic Lewis carcinoma, and highly immunogenic A20 В-cellular lymphoma. RESULTS: Our results indicated that in situ vaccination was the most effective against the highly immunogenic tumor А20. In addition, "Karanahan" demonstrated high efficiency in all types of tumors, regardless of their immunogenicity or size. CONCLUSION: "Karanahan" therapy showed higher efficacy relative to in situ vaccination with CpG oligonucleotides and anti-OX40 antibodies.


Assuntos
Antineoplásicos/imunologia , Imunoterapia/métodos , Animais , Anticorpos/imunologia , Antígenos de Diferenciação/imunologia , Antígenos de Neoplasias/imunologia , Carcinoma Pulmonar de Lewis/imunologia , Linhagem Celular Tumoral , Ciclofosfamida/imunologia , DNA/imunologia , Feminino , Linfoma/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Células-Tronco Neoplásicas/imunologia , Oligodesoxirribonucleotídeos/imunologia , Receptores OX40/imunologia , Vacinação/métodos
20.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207103

RESUMO

Ovarian cancer response to immunotherapy is limited; however, the evaluation of sensitive/resistant target treatment subpopulations based on stratification by tumor biomarkers may improve the predictiveness of response to immunotherapy. These markers include tumor mutation burden, PD-L1, tumor-infiltrating lymphocytes, homologous recombination deficiency, and neoantigen intratumoral heterogeneity. Future directions in the treatment of ovarian cancer include the utilization of these biomarkers to select ideal candidates. This paper reviews the role of immunotherapy in ovarian cancer as well as novel therapeutics and study designs involving tumor biomarkers that increase the likelihood of success with immunotherapy in ovarian cancer.


Assuntos
Imunoterapia , Neoplasias Ovarianas/terapia , Medicina de Precisão , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Terapia de Alvo Molecular , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/etiologia , Neoplasias Ovarianas/mortalidade , Medicina de Precisão/efeitos adversos , Medicina de Precisão/métodos , Resultado do Tratamento
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