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The oncology field continues its remarkable evolution over the years, with promising advances leading to innovative and individualized treatments. The development of new molecules, the identification of new therapeutic targets and the search for new sequences or combinations promise to revolutionize cancer treatments and contribute to improving survival rates, patients' quality of life and to open new perspective in oncology research. In this article, the newest data released in 2023 are reviewed.
Le domaine de l'oncologie poursuit son évolution remarquable au fil des années, avec des avancées prometteuses ouvrant la voie à des traitements novateurs et individualisés. L'élaboration de nouvelles molécules, l'identification de nouvelles cibles thérapeutiques et la recherche de nouvelles séquences ou combinaisons de traitements promettent de révolutionner la prise en charge du cancer et de contribuer à améliorer les taux de survie, la qualité de vie des patients et à ouvrir de nouvelles perspectives dans la recherche en oncologie. Dans cet article, les nouveautés parues en 2023 sont passées en revue.
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Oncologia , Qualidade de Vida , HumanosRESUMO
Frequent and with an increasing incidence in some territories, endometrial cancer is a complex disease leading to significant morbidity among affected patients. After years of research and the implementation of state-of-the-art molecular and gene assays significant breakthroughs were made. Through a better understanding of the underlying mechanisms of uterine carcinogenesis, a more precise and personalized risk stratification and the incorporation of immunotherapy, the treatment of endometrial cancer is experiencing significant improvements. This evolution, caries the genuine hope for an accurate selection of patients based on specific cancer-related characteristics, to tailor both treatment intensity and selection.
Le cancer du corps de l'utérus est une maladie fréquente, complexe et source de morbidité importante. L'implémentation de moyens de recherche de pointe, notamment l'immunothérapie, le séquençage génétique et les études moléculaires, ont abouti aux avancées discutées dans cet article. À travers une meilleure compréhension des mécanismes de la carcinogenèse endométriale, une stratification plus précise et personnalisée du risque de récidive et l'essor de l'immunothérapie, le traitement du cancer de l'utérus connaît actuellement un incontestable renouveau. Cette révolution, porteuse d'espoir, promet l'adéquation la plus exacte possible entre les traitements et l'agressivité de la maladie.
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Neoplasias do Endométrio , Feminino , Humanos , Neoplasias do Endométrio/terapia , ImunoterapiaRESUMO
The past year has brought several innovations in medical oncology, opening up promising new options for many solid tumors, both localized and metastatic. Immunotherapy, a real spearhead of emerging therapies in metastatic diseases, is seeing its use extend to adjuvant and neoadjuvant modalities, particularly in colon and lung cancers. 2022 also sees a great deal of focus on targeted therapies, as well as on antibody-drug conjugates, which creates new standards in both breast and lung cancers. Here we present the major advances in solid tumors.
L'année écoulée a apporté son lot d'innovations en oncologie médicale, ouvrant de nouvelles options prometteuses pour bon nombre de tumeurs solides, qu'elles soient localisées ou métastatiques. L'immunothérapie, véritable fer de lance des thérapies émergentes dans les maladies métastatiques, voit son usage s'étendre à des modalités adjuvantes et néoadjuvantes, notamment dans les cancers du côlon et du poumon. 2022 donne également la part belle aux thérapies ciblées mais aussi aux conjuguées anticorps-médicaments qui apportent de nouveaux standards tant pour les cancers du sein que du poumon. Nous vous présentons ici les avancées majeures concernant les tumeurs solides.
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Neoplasias Pulmonares , Oncologia , Humanos , Imunoterapia , Terapia Neoadjuvante , Neoplasias Pulmonares/terapiaRESUMO
Ovarian cancer is the first cause of death by gynecological cancer. Most of the patients are diagnosed with peritoneal carcinomatosis that represents a therapeutic challenge. Its management implies maximal cytoreductive surgery with survival benefit. Over the last three decades, several strategies of intra-peritoneal chemotherapy have been investigated. This includes intra-peritoneal adjuvant chemotherapy that is used mainly in North America, hyperthermic intraperitoneal chemotherapy (HIPEC) and more recently pressurized intraperitoneal aerosol chemotherapy (PIPAC). In the current article, we review the evidence in favor of each therapeutic approach, and we propose treatment algorithms depending on the clinical situation of ovarian cancer patients: upfront, platinum-sensitive and platinum-resistant relapse.
Le cancer de l'ovaire est la première cause de décès par cancer gynécologique. La plupart des patientes sont diagnostiquées au stade de carcinose péritonéale qui représente un défi thérapeutique. Sa prise en charge chirurgicale implique une cytoréduction maximaliste. Au cours des 30 dernières années, plusieurs stratégies de chimiothérapie intrapéritonéale ont été testées afin d'améliorer le contrôle de la carcinose péritonéale. Il s'agit des chimiothérapies intrapéritonéale adjuvante utilisée surtout en Amérique du Nord, hyperthermique intrapéritonéale (CHIP) et intrapéritonéale pressurisée en aérosols (PIPAC). Dans cet article, nous reprenons les données de la littérature sur chacune de ces trois approches thérapeutiques et proposons des algorithmes décisionnels selon la situation clinique des patientes traitées pour un cancer de l'ovaire : au diagnostic, récidive platine-sensible et platine-résistante.
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Carcinoma , Hipertermia Induzida , Neoplasias Ovarianas , Neoplasias Peritoneais , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma/terapia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgiaRESUMO
Despite COVID-19 pandemic, which is still deeply affecting world economy and global health, medical oncology specialists keep pursuing their effort for the identification of new therapeutic options to improve patients' life expectancy and quality of life. 2021 confirms the immunotherapy efficacy, alone or in combination with other modalities, across several indications. This year, we are summarizing the new approaches in the following sectors: lung, breast, melanoma, gynecological, digestive, urological and ENT areas.
En dépit de la pandémie de Covid-19 qui continue à grandement impacter l'économie mondiale et la santé, l'oncologie médicale poursuit sa quête d'identification de nouvelles options thérapeutiques ayant pour buts la prolongation de l'espérance de vie et l'amélioration de la qualité de vie de ses patients, en nombre croissant. L'année 2021 confirme également l'efficacité de l'immunothérapie, seule ou en combinaison à d'autres modalités, dans de nombreuses indications. Cette année, nous vous résumons les nouvelles approches dans les domaines suivants: poumon, sein, mélanome, sphères gynécologique, digestive, urologique et ORL.
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COVID-19 , Melanoma , Humanos , Oncologia , Pandemias , Qualidade de Vida , SARS-CoV-2RESUMO
The COVID-19 pandemic that has swept around the world in early 2020 has changed our daily practice and habits. Fortunately, however, 2020 also brings its share of new approaches and therapeutic combinations as well as new therapies. These advances are improving the outcomes and quality of life of our patients across the spectrum of oncological diseases. This article summarises the latest oncological advances and novelties for 2020 in the following tumor entities : lung, breast, digestive, gynecological, urological and ENT.
La pandémie de Covid-19 survenue début 2020 dans le monde entier aura bouleversé notre pratique quotidienne et nos habitudes. Heureusement, sur le plan thérapeutique, l'année 2020 apporte également son lot de nouvelles approches et combinaisons thérapeutiques ainsi que l'introduction de nouvelles molécules, permettant d'améliorer le pronostic vital et la qualité de vie de nos patients, dans de nombreux domaines. Cet article résume les dernières avancées et nouveautés oncologiques de l'année 2020 dans les domaines suivants : poumon, sein, sphère digestive, gynécologique, urologique et ORL.
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COVID-19 , Pandemias , Humanos , Oncologia , Neoplasias , Qualidade de Vida , SARS-CoV-2RESUMO
Driven by highly specialized medicine, research and the quest for personalization of treatments, oncology witnessed substantial advances in 2019. This year numerous treatments have consolidated their importance and broadened their indications. Multiple innovative treatments, currently under study, brought hope for future advances, while biomarkers, such as PD-L1, microsatellite instability (MSI), tumor mutational burden (TMB), BRCA1/2 gene mutations, and homologous recombination deficiency (HRD) allowed better selection and customization of available treatments. This article provides an overview of this year's advances in oncology.
Sous l'égide de la médecine hautement spécialisée, de la personnalisation des traitements et secondée par une recherche énergique, l'oncologie a connu en 2019 des avancées considérables. Cette année, de nombreux traitements ont consolidé leur importance et élargi leurs indications. L'annonce d'une pléthore de traitements novateurs, en étude, est source d'espoir pour l'avenir. Des biomarqueurs simples ou composites, tels que l'expression PD-L1, l'instabilité de microsatellite (MSI), la charge mutationnelle tumorale (TMB), les mutations des gènes BRCA1/2 ou un déficit du mécanisme de la recombinaison homologue des bases (HRD) permettent une meilleure sélection et personnalisation des traitements disponibles. Le but du présent article est de rassembler les avancées oncologiques de l'année.
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Biomarcadores Tumorais , Neoplasias , Humanos , Mutação , Neoplasias/diagnóstico , Neoplasias/terapiaRESUMO
BACKGROUND: Most ovarian cancer patients are diagnosed at a late stage with 85% of them relapsing after surgery and standard chemotherapy; for this reason, new treatments are urgently needed. Ovarian cancer has become a candidate for immunotherapy by reason of their expression of shared tumor-associated antigens (TAAs) and private mutated neoantigens (NeoAgs) and the recognition of the tumor by the immune system. Additionally, the presence of intraepithelial tumor infiltrating lymphocytes (TILs) is associated with improved progression-free and overall survival of patients with ovarian cancer. The aim of active immunotherapy, including vaccination, is to generate a new anti-tumor response and amplify an existing immune response. Recently developed NeoAgs-based cancer vaccines have the advantage of being more tumor specific, reducing the potential for immunological tolerance, and inducing robust immunogenicity. METHODS: We propose a randomized phase I/II study in patients with advanced ovarian cancer to compare the immunogenicity and to assess safety and feasibility of two personalized DC vaccines. After standard of care surgery and chemotherapy, patients will receive either a novel vaccine consisting of autologous DCs pulsed with up to ten peptides (PEP-DC), selected using an agnostic, yet personalized, epitope discovery algorithm, or a sequential combination of a DC vaccine loaded with autologous oxidized tumor lysate (OC-DC) prior to an equivalent PEP-DC vaccine. All vaccines will be administered in combination with low-dose cyclophosphamide. This study is the first attempt to compare the two approaches and to use NeoAgs-based vaccines in ovarian cancer in the adjuvant setting. DISCUSSION: The proposed treatment takes advantage of the beneficial effects of pre-treatment with OC-DC prior to PEP-DC vaccination, prompting immune response induction against a wide range of patient-specific antigens, and amplification of pre-existing NeoAgs-specific T cell clones. Trial registration This trial is already approved by Swissmedic (Ref.: 2019TpP1004) and will be registered at http://www.clinicaltrials.gov before enrollment opens.
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Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Peptídeos/imunologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Gradação de Tumores , Estadiamento de Neoplasias , Transplante AutólogoRESUMO
New targeted therapies modify therapeutic strategies for advanced stage breast and tubo-ovarian cancers. Chemotherapy and endocrine therapy remain the cornerstones of breast cancer treatment. Inhibitors of CDK4/6, mTOR and PI3K are associated with endocrine therapy to increase its effectiveness. PARP inhibitors outperform chemotherapy in BRCA1/2 mutation carriers. Immunotherapy integrates into the treatment of triple-negative cancers with very promising results. For tubo-ovarian cancers, the concept of « platinum-sensitive ¼ has been tempered since the arrival of antiangiogenic treatment and PARP inhibitors that prolong the disease control not only in patients with BRCA1/2 mutation, but also in others.
Les nouvelles thérapies ciblées modifient les stratégies thérapeutiques des cancers du sein et tubo-ovarien de stade avancé. La chimiothérapie et l'hormonothérapie restent les pierres angulaires du traitement du cancer du sein. Les inhibiteurs de CDK4/6, de mTOR et de PI3K sont associés à l'hormonothérapie pour augmenter son efficacité. Les inhibiteurs de la PARP (poly(ADP-ribose) polymérase) surpassent la chimiothérapie chez les porteuses de mutation BRCA1/2. L'immunothérapie arrive dans le traitement des cancers triple négatifs avec des résultats très prometteurs. Pour le cancer tubo-ovarien, le concept « platine-sensible ¼ est relativisé depuis l'arrivée du traitement anti-angiogénique et des inhibiteurs de la PARP qui prolongent la durée de contrôle de la maladie non seulement chez les patientes avec mutation de BRCA1/2, mais également chez les autres.
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Neoplasias da Mama , Neoplasias Ovarianas , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêuticoRESUMO
The primary treatment of ovarian cancer consists in a complete surgical debulking followed by adjuvant chemotherapy combining platinum with taxanes. Despite this treatment, patient survival has remained stable over the last 20 years. Recently, advances in the sequence, regimens, and route of administration of treatment have enhanced effectiveness and reduced toxicity. Targeted anti-angiogenic therapy and recently PARP inhibitors are now complementing standard treatment and have improved patient progression-free survival. The development of immunotherapy, alone or in combination, brings new perspectives for the future treatment of ovarian cancer.
Le traitement initial du cancer de l'ovaire consiste en une cytoréduction chirurgicale maximale, associée à une chimiothérapie adjuvante combinant les sels de platine aux taxanes. Malgré ce traitement, la survie sans récidive des patientes est restée stable ces 20 dernières années. Récemment, les avancées dans la séquence, les schémas et la voie d'administration des traitements ont permis d'optimiser leur efficacité et réduire leur toxicité. Les traitements ciblés anti-angiogéniques et récemment les inhibiteurs PARP (poly-ADP-ribose-polymérase) sont venus compléter les traitements standards et ont permis l'amélioration de la survie sans progression des patientes. Le développement de l'immunothérapie, seule ou en association avec d'autres traitements, ouvre des nouvelles perspectives pour le traitement du cancer de l'ovaire.
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The survival of patients with breast cancer has improved considerably thanks to adjuvant radiotherapy and systemic treatments. Due to the potential adverse events associated with these treatments, a de-escalation effort was undertaken concerning surgery and more recently the adjuvant treatments. Conservative breast surgery and the avoidance of axillary dissection were possible for the majority of the patients without detrimental effect on survival. New radiotherapy techniques and the consideration of cancer biology allowed to better protect the peripheral organs and even to avoid treatment in certain low-risk patients. The refinement of prognostic and predictive criteria helped reducing the use of chemotherapy and adapting the duration of endocrine therapy to the risk.
La survie des patientes ayant présenté un cancer du sein s'est considérablement améliorée grâce à la radiothérapie et aux traitements systémiques adjuvants. Au vu des effets adverses liés à ces traitements, un effort de désescalade thérapeutique a été entrepris en ce qui concerne la chirurgie et plus récemment les traitements adjuvants. La chirurgie conservatrice du sein et l'abandon du curage axillaire sont possibles pour la majorité des patientes sans altérer leur survie. Les nouvelles techniques de radiothérapie et la prise en compte de la biologie tumorale ont permis de mieux protéger les organes périphériques, voire éviter le traitement chez certaines patientes à bas risque. L'affinement des critères pronostiques et prédictifs a aidé à diminuer le recours à la chimiothérapie et adapter la durée de l'hormonothérapie au risque.
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Neoplasias da Mama/terapia , Tratamento Conservador , Seleção de Pacientes , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Tratamento Conservador/métodos , Feminino , Humanos , Futilidade Médica , Estadiamento de Neoplasias , PrognósticoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Adenoescamoso/terapia , Cesárea , Quimiorradioterapia , Terapia Neoadjuvante , Complicações Neoplásicas na Gravidez/terapia , Neoplasias do Colo do Útero/terapia , Idoso , Antineoplásicos/uso terapêutico , Braquiterapia/métodos , Carboplatina/administração & dosagem , Carcinoma Adenoescamoso/diagnóstico por imagem , Cisplatino/uso terapêutico , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Período Pós-Parto , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Resultado da Gravidez , Segundo Trimestre da Gravidez , Radioterapia de Intensidade Modulada/métodos , Ultrassonografia , Neoplasias do Colo do Útero/diagnóstico por imagemRESUMO
BACKGROUND: Oral anticancer therapies such as protein kinase inhibitors (PKIs) are increasingly prescribed in cancer care. We aimed to evaluate the impact of a pharmacist-led interprofessional medication adherence program (IMAP) on patient implementation (dosing history), persistence (time until premature cessation of the treatment) and adherence to 27 PKIs prescribed for various solid cancers, as well as the impact on patients' beliefs about medicines (BAM) and quality of life (QoL). METHODS: Patients (n = 118) were randomized 1:1 into two arms. In the intervention arm, pharmacists supported patient adherence through monthly electronic and motivational feedback, including educational, behavioral and affective components, for 12 months. The control arm received standard care plus EM without intervention. All PKIs were delivered in electronic monitors (EMs). Medication implementation and adherence were compared between groups using generalized estimating equation models, in which relevant covariables were included; persistence was compared with KaplanâMeier curves. Information on all treatment interruptions was compiled for the analysis. Questionnaires to evaluate BAM and QoL were completed among patients who refused and those who accepted to participate at inclusion, 6 and 12 months post-inclusion or at study exit. RESULTS: Day-by-day PKI implementation was consistently higher and statistically significant in the intervention arm (n = 58) than in the control arm (n = 60), with 98.1% and 95.0% (Δ3.1%, 95% confidence interval (CI) of the difference 2.5%; 3.7%) implementation at 6 months, respectively. The probabilities of persistence and adherence were not different between groups, and no difference was found between groups for BAM and QoL scores. No difference in BAM or QoL was found among patients who refused versus those who participated. The intervention benefited mostly men (at 6 months, Δ4.7%, 95% CI 3.4%; 6.0%), those younger than 60 years (Δ4.0%, 95% CI 3.1%; 4.9%), those who had initiated PKI more than 60 days ago before inclusion (Δ4.5%, 95% CI 3.6%; 5.4%), patients without metastasis (Δ4.5%, 95% CI 3.4%; 5.7%), those who were diagnosed with metastasis more than 2 years ago (Δ5.3%, 95% CI 4.3%; 6.4%) and those who had never used any adherence tool before inclusion (Δ3.8%, 95% CI 3.1%; 4.5%). CONCLUSIONS: The IMAP, led by pharmacists in the context of an interprofessional collaborative practice, supported adherence, specifically implementation, to PKIs among patients with solid cancers. To manage adverse drug events, PKI transient interruptions are often mandated as part of a strategy for treatment and adherence optimization according to guidelines. Implementation of longer-term medication adherence interventions in the daily clinic may contribute to the improvement of progression-free survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT04484064.
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Antineoplásicos , Adesão à Medicação , Farmacêuticos , Qualidade de Vida , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Administração Oral , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/administração & dosagemRESUMO
The burden of the decisions related to cancer management is the reason why doctors are trying to use the best indicators to manage doubt and uncertainty, as well as to improve treatment targeting. These indicators are called tumor markers. They may assist in the diagnostic process and help in establishing the prognosis. They may be used for screening an asymptomatic disease, early detection of recurrent disease and mainly follow-up during cancer therapies. The better understanding of carcinogenesis coupled to technical improvements led to the discovery of new markers. They target cellular or genetic abnormalities and revisit classic cancer classification while some predict disease response to targeted therapies. This is the era of personalized oncology.
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Biomarcadores Tumorais , Neoplasias/diagnóstico , Biomarcadores Tumorais/análise , Humanos , Neoplasias/química , Neoplasias/terapiaRESUMO
Posterior reversible encephalopathy syndrome is a rare neurological disorder, the diagnosis of which is based on the combination of clinical and radiological findings. It can be associated with many patient-related conditions such as autoimmune disorders or can be provoked by toxins or medication. We report the case of a 70-year-old patient, known for International Federation of Gynecology and Obstetrics stage IVB, high-grade serous ovarian carcinoma, who was diagnosed with a posterior reversible encephalopathy syndrome while on bevacizumab and olaparib maintenance treatment.
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Borderline ovarian tumors (BOTs) account for 10-20% of epithelial ovarian neoplasms. They are characterized by their lack of destructive stromal invasion. In comparison to invasive ovarian cancers, BOTs occur in younger patients and have better outcome. Serous borderline ovarian tumor (SBOT) represents the most common subtype of BOT. Complete surgical staging is the current standard management but fertility-sparing surgery is an option for SBOT patients who are at reproductive age. While most cases of SBOTs have an indolent course with favorable prognosis, late recurrence and malignant transformation can occur, usually in the form of low-grade serous carcinoma (LGSC). Thus, assessment of the recurrence risk is essential for the management of those patients. SBOTs can be associated with lymph node involvement (LNI) in up to 30% of patients who undergo lymph node dissection at diagnosis, and whether LNI affects prognosis is controversial. The present review suggests that recurrent SBOTs with LNI have poorer oncological outcomes and highlights the biases due to the scarcity of reports in the literature. Preventing SBOTs from recurring and becoming invasive overtime and a more profound understanding of the underlying mechanisms at play are necessary.
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The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib is administered orally and cyclically, causing medication adherence challenges. We evaluated components of adherence to palbociclib, its relationship with pharmacokinetics (PK), and drug-induced neutropenia. Patients with metastatic breast cancer (MBC) receiving palbociclib, delivered in electronic monitors (EM), were randomized 1:1 to an intervention and a control group. The intervention was a 12-month interprofessional medication adherence program (IMAP) along with monthly motivational interviews by a pharmacist. Implementation adherence was compared between groups using generalized estimating equation models, in which covariates were included. Model-based palbociclib PK and neutrophil profiles were simulated under real-life implementation scenarios: (1) optimal, (2) 2 doses omitted and caught up at cycle end. At 6 months, implementation was slightly higher and more stable in the intervention (n = 19) than in the control (n = 19) group, 99.2% and 97.3% (Δ1.95%, 95% CI 1.1−2.9%), respectively. The impact of the intervention was larger in patients diagnosed with MBC for >2 years (Δ3.6%, 95% CI 2.1−5.4%), patients who received >4 cycles before inclusion (Δ3.1%, 95% CI 1.7−4.8%) and patients >65 (Δ2.3%, 95% CI 0.8−3.6%). Simulations showed that 25% of patients had neutropenia grade ≥3 during the next cycle in scenario 1 versus 30% in scenario 2. Education and monitoring of patient CDK4/6i cycle management and adherence along with therapeutic drug monitoring can help clinicians improve prescription and decrease toxicity.
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Background: The use of circulating cDC1 to generate anti-cancer vaccines is among the most promising approaches to overcome the limited immunogenicity and clinical efficacy of monocyte-derived DC. However, the recurrent lymphopenia and the reduction of DC numbers and functionality in patients with cancer may represent an important limitation of such approach. In patients with ovarian cancer (OvC) that had received chemotherapy, we previously showed that cDC1 frequency and function were reduced. Methods: We recruited healthy donors (HD, n=7) and patients with OvC at diagnosis and undergoing interval debulking surgery (IDS, n=6), primary debulking surgery (PDS, n=6) or at relapse (n=8). We characterized longitudinally phenotypic and functional properties of peripheral DC subsets by multiparametric flow cytometry. Results: We show that the frequency of cDC1 and the total CD141+ DC capacity to take up antigen are not reduced at the diagnosis, while their TLR3 responsiveness is partially impaired in comparison with HD. Chemotherapy causes cDC1 depletion and increase in cDC2 frequency, but mainly in patients belonging to the PDS group, while in the IDS group both total lymphocytes and cDC1 are preserved. The capacity of total CD141+ DC and cDC2 to take up antigen is not impacted by chemotherapy, while the activation capacity upon Poly(I:C) (TLR3L) stimulation is further decreased. Conclusions: Our study provides new information about the impact of chemotherapy on the immune system of patients with OvC and sheds a new light on the importance of considering timing with respect to chemotherapy when designing new vaccination strategies that aim at withdrawing or targeting specific DC subsets.
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Células Dendríticas , Recidiva Local de Neoplasia , Neoplasias Ovarianas , Feminino , Humanos , Imunoterapia , Monócitos , Neoplasias Ovarianas/tratamento farmacológico , Células Dendríticas/imunologiaRESUMO
We have previously shown that vaccination with tumor-pulsed dendritic cells amplifies neoantigen recognition in ovarian cancer. Here, in a phase 1 clinical study ( NCT01312376 /UPCC26810) including 19 patients, we show that such responses are further reinvigorated by subsequent adoptive transfer of vaccine-primed, ex vivo-expanded autologous peripheral blood T cells. The treatment is safe, and epitope spreading with novel neopeptide reactivities was observed after cell infusion in patients who experienced clinical benefit, suggesting reinvigoration of tumor-sculpting immunity.
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Neoplasias Ovarianas , Vacinas , Humanos , Feminino , Neoplasias Ovarianas/terapia , Transferência Adotiva , Vacinação , Linfócitos TRESUMO
BACKGROUND: Screening and treatment of latent tuberculosis infection (LTBI) in asylum seekers (AS) may prevent future cases of tuberculosis. As the screening with Interferon Gamma Release Assay (IGRA) is costly, the objective of this study was to assess which factors were associated with LTBI and to define a score allowing the selection of AS with the highest risk of LTBI. METHODS: In across-sectional study, AS seekers recently arrived in Vaud County, after screening for tuberculosis at the border were offered screening for LTBI with T-SPOT.TB and questionnaire on potentially risk factors. The factors associated with LTBI were analyzed by univariate and multivariate regression. RESULTS: Among 393 adult AS, 98 (24.93%) had a positive IGRA response, five of them with active tuberculosis previously undetected. Six factors associated with LTBI were identified in multivariate analysis: origin, travel conditions, marital status, cough, age and prior TB exposure. Their combination leads to a robust LTBI predictive score. CONCLUSIONS: The prevalence of LTBI and active tuberculosis in AS is high. A predictive score integrating six factors could identify the asylum seekers with the highest risk for LTBI.