Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.660
Filtrar
1.
Rev Med Suisse ; 16(709): 1853-1859, 2020 Oct 07.
Artigo em Francês | MEDLINE | ID: mdl-33026727

RESUMO

A quarter of cutaneous melanomas occur on the head and neck. Despite close collaboration between the dermatology, oncology, pathology, nuclear medicine and otorhinolaryngology departments, the survival of patients presenting with this type of melanomas remains inferior to that of other parts of the body. The morbidity of head and neck surgery significantly alters the quality of life. Therefore, specific multidisciplinary expertise is required. We present here the specificities of ENT management.


Assuntos
Orelha , Neoplasias de Cabeça e Pescoço/terapia , Melanoma/terapia , Nariz , Faringe , Papel do Médico , Neoplasias Cutâneas/terapia , Humanos , Qualidade de Vida
2.
Nat Commun ; 11(1): 4909, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999291

RESUMO

Effectively activating macrophages against cancer is promising but challenging. In particular, cancer cells express CD47, a 'don't eat me' signal that interacts with signal regulatory protein alpha (SIRPα) on macrophages to prevent phagocytosis. Also, cancer cells secrete stimulating factors, which polarize tumor-associated macrophages from an antitumor M1 phenotype to a tumorigenic M2 phenotype. Here, we report that hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants with significantly increased affinity to CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting M2-to-M1 repolarization within tumor microenvironment, significantly preventing both local recurrence and distant metastasis in malignant melanoma models. Furthermore, by loading a stimulator of interferon genes (STING) agonist, hNVs lead to potent tumor inhibition in a poorly immunogenic triple negative breast cancer model. hNVs are safe, stable, drug loadable, and suitable for genetic editing. These properties, combined with the capabilities inherited from source cells, make hNVs an attractive immunotherapy.


Assuntos
Micropartículas Derivadas de Células/imunologia , Imunoterapia/métodos , Macrófagos/imunologia , Melanoma/terapia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias de Mama Triplo Negativas/terapia , Animais , Antígeno CD47/metabolismo , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Melanoma/imunologia , Melanoma/secundário , Proteínas de Membrana/agonistas , Proteínas de Membrana/imunologia , Camundongos , Nanopartículas/administração & dosagem , Recidiva Local de Neoplasia/imunologia , Nucleotídeos Cíclicos/administração & dosagem , Receptores Imunológicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Neoplasias de Mama Triplo Negativas/imunologia , Evasão Tumoral/efeitos dos fármacos , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia
3.
Cancer Treat Rev ; 89: 102083, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32736188

RESUMO

Melanoma brain metastases (MBM) are common and associated with a particularly poor prognosis; they directly cause death in 60-70% of melanoma patients. In the past, systemic treatments have shown response rates around 5%, whole brain radiation as standard of care has achieved a median overall survival of approximately three months. Recently, the combination of immune checkpoint inhibitors and combinations of MAP-kinase inhibitors both have shown very promising response rates of up to 55% and 58%, respectively, and improved survival. However, current clinical evidence is based on multi-cohort studies only, as prospectively randomized trials have been carried out rarely in MBM, independently whether investigating systemic therapy, radiotherapy or surgical techniques. Here, an interdisciplinary expert team reviewed the outcome of prospectively conducted clinical studies in MBM, identified evidence gaps and provided recommendations for the diagnosis, treatment, outcome evaluation and monitoring of MBM patients. The recommendations refer to four distinct scenarios: patients (i) with 'brain-only' disease, (ii) with oligometastatic asymptomatic intra- and extracranial disease, (iii) with multiple asymptomatic metastases, and (iv) with multiple symptomatic MBM or leptomeningeal disease. Changes in current management recommendations comprise the use of immunotherapy - preferably combined anti-CTLA-4/PD-1-immunotherapy - in asymptomatic MBM minus/plus stereotactic radiosurgery which remains the mainstay of local brain therapy being safe and effective. Adjuvant whole-brain radiotherapy provides no clinical benefit in oligometastatic MBM. Among the systemic therapies, combined MAPK-kinase inhibition provides, in BRAFV600-mutated patients with rapidly progressing or/and symptomatic MBM, an alternative to combined immunotherapy.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Melanoma/patologia , Melanoma/terapia , Animais , Neoplasias Encefálicas/diagnóstico , Ensaios Clínicos como Assunto , Estudos de Coortes , Terapia Combinada , Humanos , Melanoma/diagnóstico , Equipe de Assistência ao Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
4.
Value Health ; 23(7): 898-906, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762992

RESUMO

OBJECTIVES: We evaluated how next generation sequencing (NGS) can modify care pathways in an observational impact study in France. METHODS: All patients with lung cancer, colorectal cancer, or melanoma who had NGS analyses of somatic genomic alterations done in 1 of 7 biomolecular platforms certified by the French National Cancer Institute (INCa) between 2013 and 2016 were eligible. We compared patients' pathways before and after their NGS results. Endpoints consisted of the turnaround time in obtaining results, the number of patients with at least 1 genomic alteration identified, the number of actionable alterations, the impact of the genomic multidisciplinary tumor board on care pathways, the number of changes in the treatment plan, and the survival outcome up to 1 year after NGS analyses. RESULTS: 1213 patients with a request for NGS analysis were included. NGS was performed for 1155 patients, identified at least 1 genomic alteration for 867 (75%), and provided an actionable alteration for 614 (53%). Turnaround time between analyses and results was on average 8 days (Min: 0; Max: 95) for all cancer types. Before NGS analysis, 33 of 614 patients (5%) were prescribed a targeted therapy compared with 54 of 614 patients (8%) after NGS analysis. Proposition of inclusion in clinical trials with experimental treatments increased from 5% (n = 31 of 614) before to 28% (n = 178 of 614) after NGS analysis. Patients who benefited from a genotype matched treatment after NGS analysis tended to have a better survival outcome at 1 year than patients with nonmatched treatment: 258 days (±107) compared with 234 days (±106), (P = .41). CONCLUSIONS: NGS analyses resulted in a change in patients' care pathways for 20% of patients (n = 232 of 1155).


Assuntos
Neoplasias Colorretais/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Melanoma/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/terapia , Feminino , França , Genômica/métodos , Acesso aos Serviços de Saúde , Humanos , Neoplasias Pulmonares/terapia , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Estudos Retrospectivos , Sobrevida , Fatores de Tempo , Adulto Jovem
5.
Proc Natl Acad Sci U S A ; 117(33): 20159-20170, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32747553

RESUMO

Although immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment, many patients do not respond or develop resistance to ICB. N6 -methylation of adenosine (m6A) in RNA regulates many pathophysiological processes. Here, we show that deletion of the m6A demethylase Alkbh5 sensitized tumors to cancer immunotherapy. Alkbh5 has effects on m6A density and splicing events in tumors during ICB. Alkbh5 modulates Mct4/Slc16a3 expression and lactate content of the tumor microenvironment and the composition of tumor-infiltrating Treg and myeloid-derived suppressor cells. Importantly, a small-molecule Alkbh5 inhibitor enhanced the efficacy of cancer immunotherapy. Notably, the ALKBH5 gene mutation and expression status of melanoma patients correlate with their response to immunotherapy. Our results suggest that m6A demethylases in tumor cells contribute to the efficacy of immunotherapy and identify ALKBH5 as a potential therapeutic target to enhance immunotherapy outcome in melanoma, colorectal, and potentially other cancers.


Assuntos
Homólogo AlkB 5 da RNA Desmetilase/metabolismo , Vacinas Anticâncer/imunologia , Lactatos/metabolismo , Melanoma/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T Reguladores/fisiologia , Homólogo AlkB 5 da RNA Desmetilase/genética , Anticorpos , Citocinas/genética , Citocinas/metabolismo , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/terapia , Metiltransferases/genética , Metiltransferases/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Células Supressoras Mieloides/fisiologia , Sítios de Splice de RNA , Processamento de RNA , Simportadores/genética , Simportadores/metabolismo , Transcriptoma , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Medicine (Baltimore) ; 99(29): e21329, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702928

RESUMO

In BRAF wild type advanced melanoma, immune checkpoint blockers such as anti-PD1 (anti-programmed cell death 1) are usually continued beyond progression for a hypothetical rare further response. Chemotherapy as a second-line option is considered ineffective by many practitioners based on historical data. Continuing anti-PD1 beyond progression has a high health-economic impact and is not recommended by the FDA. This study aimed to describe the efficacy and survival of advanced melanoma patients who received second-line (or more) chemotherapy after immunotherapy failure.This was a retrospective single center study conducted in a French University Hospital during an 11-month period. All advanced melanoma patients treated with chemotherapy after immunotherapy failure were included.Eighteen patients were analyzed. Therapeutic response to chemotherapy was evaluable in 16 patients: partial response was achieved in 3/16 (19%), stable disease in 1/16 (6%) and progressive disease in 12/16 (75%). Median overall survival from chemotherapy start was 12 months. Median progression-free survival was 5.4 months. The 6-month overall survival rate was 81% and the 6-month progression-free survival rate was 40%.Although the disease control rate with chemotherapy was low (25%), survival data in our study are far superior to those previously published. This could be linked to a high proportion of patients treated with anti-PD1 just prior to chemotherapy, which may suggest a potential synergy between immunotherapy and chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Imunoterapia/métodos , Melanoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento
7.
Clin Ter ; 171(4): e283-e287, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614358

RESUMO

An early identification of non-responders in oncology is of crucial importance to rapidly switch treatment regimens. Here we report a positron emission tomography, (PET)-guided switch from immunotherapy to targeted therapy in a patient affected by metastatic melanoma. We describe the case of a 78-years-old male patient diagnosed with nodular melanoma, submitted to baseline PET/CT with 18fluorodeoxyglucose (18F-FDG) that showed cutaneous and skeletal metastases (stage IV). The patients started immunotherapy with pembrolizumab. A PET/CT performed 3 months after the start of immunotherapy demonstrated progressive metabolic disease both at skeletal and cutaneous level, confirmed also by the biopsy. As patients resulted positive for BRAF V600k mutation, treatment regimen was rapidly switched to combined anti-BRAF/MEK targeted therapy. The PET/CT performed 3 months later, showed almost complete metabolic response. Ten months after the beginning of targeted therapy, the patient continues to present a durable metabolic response. PET/CT with 18F-FDG may help in monitoring the response to treatment in metastatic melanoma thus defining personalized therapeutic pathways.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Imunoterapia , Melanoma/terapia , Neoplasias Cutâneas/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Imidazóis/uso terapêutico , Imunoterapia/métodos , Masculino , Oximas/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons , Inibidores de Proteínas Quinases/uso terapêutico , Piridonas/uso terapêutico , Pirimidinonas/uso terapêutico , Resultado do Tratamento
8.
Cancer Treat Rev ; 88: 102060, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32619863

RESUMO

Phenotypic plasticity of malignant melanoma is a well-known phenomenon. Several translational studies and small case series have reported this clinical and biological entity, particularly in metastatic melanoma, showing frequent aberrant expression of non-melanocytic differentiation markers of different lineages, posing remarkable challenges due to several alternative differential diagnoses including undifferentiated carcinoma and sarcomas. When melanoma loses its typical morpho-phenotype by routinely used diagnostic immunohistochemical markers, it is defined as "dedifferentiated melanoma". Historically, this process was closely related to diagnostic interpretative difficulties. In recent years, however, dedifferentiation has been increasingly recognized as an important biological phenomenon that demonstrates the phenotypic and genetic plasticity of melanoma, and specifically the non-irreversibility of the multistep cancerogenesis. Furthermore, dedifferentiation emerged as a general hallmark of cancer evolution and a common denominator of cross-resistance to both targeted and immunotherapy. In this review, we summarize the histopathological features, the genetic and epigenetic bases underlying the dedifferentiated phenotype in melanomas and provide additional support that dedifferentiation is a mechanism of resistance to immunotherapy and targeted therapy.


Assuntos
Melanoma/genética , Melanoma/terapia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Animais , Desdiferenciação Celular/fisiologia , Reprogramação Celular/fisiologia , Epigênese Genética , Humanos , Melanoma/patologia , Neoplasias Cutâneas/patologia
9.
Nature ; 585(7823): 107-112, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32728218

RESUMO

Treating patients who have cancer with vaccines that stimulate a targeted immune response is conceptually appealing, but cancer vaccine trials have not been successful in late-stage patients with treatment-refractory tumours1,2. We are testing melanoma FixVac (BNT111)-an intravenously administered liposomal RNA (RNA-LPX) vaccine, which targets four non-mutated, tumour-associated antigens that are prevalent in melanoma-in an ongoing, first-in-human, dose-escalation phase I trial in patients with advanced melanoma (Lipo-MERIT trial, ClinicalTrials.gov identifier NCT02410733). We report here data from an exploratory interim analysis that show that melanoma FixVac, alone or in combination with blockade of the checkpoint inhibitor PD1, mediates durable objective responses in checkpoint-inhibitor (CPI)-experienced patients with unresectable melanoma. Clinical responses are accompanied by the induction of strong CD4+ and CD8+ T cell immunity against the vaccine antigens. The antigen-specific cytotoxic T-cell responses in some responders reach magnitudes typically reported for adoptive T-cell therapy, and are durable. Our findings indicate that RNA-LPX vaccination is a potent immunotherapy in patients with CPI-experienced melanoma, and suggest the general utility of non-mutant shared tumour antigens as targets for cancer vaccination.


Assuntos
Antineoplásicos/uso terapêutico , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Melanoma/imunologia , Melanoma/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , RNA Neoplásico/genética , Linfócitos T/imunologia , Antígenos de Neoplasias/imunologia , Antineoplásicos/farmacologia , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/efeitos adversos , Terapia Combinada , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Estadiamento de Neoplasias , Linfócitos T/citologia , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia , Vacinação
10.
Scand J Immunol ; 92(4): e12927, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32640053

RESUMO

Malignant melanoma has seen monumental changes in treatment options the last decade from the very poor results of dacarbazine treatment to the modern-day use of targeted therapies and immune checkpoint inhibitors. Melanoma has a high mutational burden making it more capable of evoking immune responses than many other tumours. Even when considering double immune checkpoint blockade with anti-CTLA-4 and anti-PD-1, we still have far to go in melanoma treatment as 50% of patients with metastatic disease do not respond to current treatment. Alternative immunotherapy should therefore be considered. Since melanoma has a high mutational burden, it is considered more immunogenic than many other tumours. T cell receptor (TCR) therapy could be a possible way forward, either alone or in combination, to improve the response rates of this deadly disease. Melanoma is one of the cancers where TCR therapy has been frequently applied. However, the number of antigens targeted remains fairly limited, although advanced personalized therapies aim at also targeting private mutations. In this review, we look at possible aspects of targeting TCR therapy towards melanoma and provide an implication of its use in the future.


Assuntos
Imunoterapia/métodos , Melanoma/imunologia , Melanoma/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Animais , Humanos
12.
Anticancer Res ; 40(6): 3411-3415, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487638

RESUMO

BACKGROUND/AIM: Acral lentiginous melanoma (ALM) is the least common subtype of cutaneous melanoma and typically occurs on the palms, soles, and nails. Tumor characteristics and disease severity in the US population are not well understood. Our aim was to analyze the characteristics of ALM of the extremities. PATIENTS AND METHODS: We queried the National Cancer Database to identify patients with the diagnosis of ALM and common malignant melanoma located in the extremities (CMME). We compared demographic, tumor, and treatment characteristics between patients with ALM and those with CMME. Statistical analysis was performed with chi-squared test and multivariate logistic regression models. RESULTS: We identified 5,203 patients with ALM and 118,485 with CMME. When compared with patients with CMME, those with ALM were more likely to be older than 80. years at diagnosis [odds ratio (OR)=2.85, 95% confidence intervaI (CI)=2.12-3.82; p<0.001], have stage III disease (OR=4.22, 95% CI=1.47-12.16; p=0.01), and have ulceration (OR=1.52, 95% CI=1.33-1.74; p<0.001). Moreover, patients with ALM were less likely to have a mitotic count of 1/mm2 or greater (OR=0.57, 95% CI=0.48-0.67; p<0.001). No statistical difference was found for sex, lymph node involvement, regression, and use of surgery, radiotherapy, and immunotherapy between groups. CONCLUSION: Age, disease stage, ulceration, and mitotic count are independent factors associated with ALM. Knowledge of the disease characteristics may allow for better diagnosis and understanding of disease pathophysiology.


Assuntos
Pé/patologia , Mãos/patologia , Melanoma/diagnóstico , Melanoma/epidemiologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Bases de Dados Factuais , Feminino , Humanos , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Estudos Retrospectivos , Neoplasias Cutâneas/terapia , Resultado do Tratamento , Adulto Jovem
16.
J Surg Oncol ; 122(3): 555-561, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32441371

RESUMO

BACKGROUND AND OBJECTIVES: Metastasectomy for melanoma provides durable disease control in carefully selected patients. Similarly, BRAF-targeted and immune checkpoint inhibition has improved median overall survival (OS) in metastatic patients. We hypothesized that there is an increasing role for metastasectomy in melanoma patients responding to these therapies. METHODS: Retrospective analysis of a prospectively maintained database identified 128 patients with stage IV melanoma who received targeted molecular and/or checkpoint inhibitors at an academic institution from 2006 to 2017. Records were reviewed to characterize clinicopathologic characteristics, response to treatment, and intent of surgery for those who underwent metastasectomy. OS was analyzed by the Kaplan-Meier method. RESULTS: Median OS from stage IV diagnosis was 31.3 months. A total of 81 patients received checkpoint inhibitors, 11 received targeted inhibitors, and 36 received both. A total of 73 patients underwent metastasectomy. Indications for surgery included the intent to render disease-free (54%), palliation (34%), and diagnostic confirmation (11%). Responders to systemic therapy who underwent metastasectomy had improved OS compared to responders who did not (84.3 vs. 42.9 months, P = .018). CONCLUSIONS: Metastasectomy for melanoma is associated with improved OS in patients that respond to targeted molecular or immunotherapy. Resection should be strongly considered in this cohort as multimodality treatment results in excellent OS.


Assuntos
Melanoma/secundário , Melanoma/terapia , Feminino , Humanos , Imunoterapia/métodos , Masculino , Melanoma/mortalidade , Melanoma/cirurgia , Metastasectomia , Terapia de Alvo Molecular/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos
18.
Internist (Berl) ; 61(7): 669-675, 2020 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-32462249

RESUMO

Although cutaneous melanoma accounts for only about 4% of all skin cancers (including nonmelanocytic skin cancer), it is responsible for 80% of all deaths caused by skin cancer. The introduction of immune checkpoint inhibitors led to a significant improvement in long-term survival of patients in an advanced stage regardless of BRAF mutation status. In addition to targeted therapy for patients with BRAF-mutated melanoma, immunotherapies are the therapies of choice in advanced stages and, since 2018, also in the adjuvant setting. The effectiveness of combination therapies and sequences of targeted and immunotherapies are currently being tested.


Assuntos
Imunoterapia , Melanoma/terapia , Terapia de Alvo Molecular/métodos , Neoplasias Cutâneas/terapia , Terapia Combinada , Humanos , Melanoma/patologia , Neoplasias Cutâneas/patologia
19.
Cancer Immunol Immunother ; 69(9): 1823-1832, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350591

RESUMO

Radiotherapy can elicit abscopal effects in non-irradiated metastases, particularly under immune checkpoint blockade (ICB). We report on two elderly patients with oligometastatic melanoma treated with anti-PD-1 and stereotactic body radiation therapy (SBRT). Before treatment, patient 1 showed strong tumor infiltration with exhausted CD8+ T cells and high expression of T cell-attracting chemokines. This patient rapidly mounted a complete response, now ongoing for more than 4.5 years. Patient 2 exhibited low CD8+ T cell infiltration and high expression of immunosuppressive arginase. After the first SBRT, his non-irradiated metastases did not regress and new metastases occurred although neoepitope-specific and differentiation antigen-specific CD8+ T cells were detected in the blood. A second SBRT after 10 months on anti-PD-1 induced a radiologic complete response correlating with an increase in activated PD-1-expressing CD8 T cells. Apart from a new lung lesion, which was also irradiated, this deep abscopal response lasted for more than 2.5 years. However, thereafter, his disease progressed and the activated PD-1-expressing CD8 T cells dropped. Our data suggest that oligometastatic patients, where a large proportion of the tumor mass can be irradiated, are good candidates to improve ICB responses by RT, even in the case of an unfavorable pretreatment immune signature, after progression on anti-PD-1, and despite advanced age. Besides repeated irradiation, T cell epitope-based immunotherapies (e.g., vaccination) may prolong antitumor responses even in patients with unfavorable pretreatment immune signature.


Assuntos
Melanoma/imunologia , Melanoma/radioterapia , Receptor de Morte Celular Programada 1/imunologia , Idoso , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Feminino , Humanos , Imunoterapia/métodos , Masculino , Melanoma/terapia , Radiocirurgia/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA