NY-ESO-1-Specific Circulating CD4+ T Cells in Ovarian Cancer Patients Are Prevalently TH1 Type Cells Undetectable in the CD25+FOXP3+Treg Compartment

Spontaneous CD4+ T-cell responses to the tumor-specific antigen NY-ESO-1 (ESO) are frequently found in patients with epithelial ovarian cancer (EOC). If these responses are of effector or/and Treg type, however, has remained unclear. Here, we have used functional approaches together with recently developed MHC class II/ESO tetramers to assess the frequency, phenotype and function of ESO-specific cells in circulating lymphocytes from EOC patients. We found that circulating ESO-specific CD4+ T cells in EOC patients with spontaneous immune responses to the antigen are prevalently TH1 type cells secreting IFN-γ but no IL-17 or IL-10 and are not suppressive. We detected tetramer+ cells ex vivo, at an average frequency of 1∶25000 memory cells, that is, significantly lower than in patients immunized with an ESO vaccine. ESO tetramer+ cells were mostly effector memory cells at advanced stages of differentiation and were not detected in circulating CD25+FOXP3+Treg. Thus, spontaneous CD4+ T-cell responses to ESO in cancer patients are prevalently of TH1 type and not Treg. Their relatively low frequency and advanced differentiation stage, however, may limit their efficacy, that may be boosted by immunogenic ESO vaccines

EXPERIENCE FRANCAISE DU PROTOCOLE BCIRG 101. ETUDE DE 10 PATIENTES PRESENTANT UN CANCER DU SEIN EN PREMIERE LIGNE METASTATIQUE,TRAITEES PAR L'ASSOCIATION DOCETAXEL-CISPLATINE ET TRASTUZUMAB

NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Le carnet de surveillance (un outil essentiel pour la surveillance alternée des femmes traitées pour un cancer du sein non métastasique)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Traduction et adaptation française du « Return to Work Self-Efficacy’ scale – 11 items » chez des patients diagnostiqués d’un cancer

National audienceINTRODUCTION: The self-efficacy to return to work is a major psychological factor of the return to work of patients diagnosed with a cancer. However, french investigations in this field do not take this dimension into account due to the lack of a suitable tool for its assessment. The objective of this study was to provide a french translation and adaptation of the \"Return to Work Self-Efficacy’ scale - 11 items\" (RTWSE-11), validated in dutch language in its original version. METHODS: After translation-back translation steps, completed by experts’ consensus meetings, interviews were conducted with thirteen patients diagnosed with cancer in order to evaluate the degree of clarity, simplicity and ambiguity or the various elements of the french version of the RTW-SE-11. RESULTS: The main modifications inherent to the french adaptation of the questionnaire concerned the modalities of the Likert scale and the inversion of three negative items into positive items. DISCUSSION: The french translation and adaptation of the RTWSE-11 was particularly faithful to the semantic, idiomatic, functional, experiential, conceptual and operational aspects of the original version. Future work can therefore focus on the psychometrics evaluations of the questionnaire. However, this tool can already be used in clinical practice to establish an initial assessment of the ability of patients diagnosed with cancer to return to work

Hormonoresistance in advanced breast cancer: a new revolution in endocrine therapy

Endocrine therapy is the mainstay of treatment of estrogen-receptor-positive (ER+) breast cancer with an overall survival benefit. However, some adaptive mechanisms in the tumor emerge leading to the development of a resistance to this therapy. A better characterization of this process is needed to overcome this resistance and to develop new tailored therapies. Mechanisms of resistance to hormone therapy result in activation of transduction signal pathways, including the cell cycle regulation with cyclin D/CDK4/6/Rb pathway. The strategy of combined hormone therapy with targeted agents has shown an improvement of progression-free survival (PFS) in several phase II or III trials, including three different classes of drugs: mTOR inhibitors, PI3K and CDK4/6 inhibitors. A recent phase III trial has shown that fulvestrant combined with a CDK 4/6 inhibitor doubles PFS in aromatase inhibitor-pretreated postmenopausal ER+ breast cancer. Other combinations are ongoing to disrupt the interaction between PI3K/AKT/mTOR and cyclin D/CDK4/6/Rb pathways. Despite these successful strategies, reliable and reproducible biomarkers are needed. Tumor genomics are dynamic over time, and blood-based biomarkers such as circulating tumor DNA represent a major hope to elucidate the adaptive mechanisms of endocrine resistance. The optimal combinations and biomarkers to guide this strategy need to be determined

An open-label, dose-escalation study to evaluate the safety and pharmacokinetics of CEP-9722 (a PARP-1 and PARP-2 inhibitor) in combination with gemcitabine and cisplatin in patients with advanced solid tumors

Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors may potentiate chemotherapy by hindering DNA damage repair pathways. CEP-9722 is the prodrug of CEP-8983, a selective inhibitor of PARP-1 and PARP-2. Preclinical studies and a prior phase 1 study suggested that CEP-9722 may cause less myelosuppression than has been observed with other oral PARP inhibitors. The primary objective of this study was to determine the maximum-tolerated dose of CEP-9722 in combination with gemcitabine and cisplatin in patients with advanced solid tumors. All patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1250 mg/m2 on days 1 and 8 of a 21-day cycle. Patients who completed one cycle of chemotherapy alone continued chemotherapy in combination with CEP-9722 150, 200, 300, or 400mg orally twice daily on days 2-7, with dose-limiting toxicity assessed in cycle 2. Patients experiencing clinical benefit could continue treatment until disease progression or unacceptable toxicity. Thirty-two patients enrolled; 18 patients completed cycle 1 and received chemotherapy plus CEP-9722. The median (range) treatment administration with CEP-9722 was five (1-12) cycles. No patient experienced dose-limiting toxicity with CEP-9722 treatment. Grade 3/4 hematologic adverse events included neutropenia (28%) and leukopenia (11%); adverse events led to discontinuation in 33% of patients. One patient achieved complete response, three had partial responses, and 11 had stable disease; however, the relative contribution of CEP-9722 and/or the chemotherapeutic agents cannot be determined from this single-arm design. This study was discontinued before determination of the maximum-tolerated dose because of highly variable CEP-8983 exposure in all cohorts and toxicity, particularly chemotherapy-induced myelosuppression.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

<i>Ex vivo</i> assessment of ESO-specific CD4⁺ T cells using DR52b/ESO tetramers.

<p>CD4⁺ T cells from DR52b⁺ healthy donors (HD) and patients were stained <i>ex vivo</i> with DR52b/ESO_119–143 tetramers and mAb specific for CD45RA, CD25, CD127, CCR7 and CD27 and analyzed by flow cytometry. <b>A</b>. Dot plots for one HD and one EOC patient are shown. Numbers in dot plots correspond to the percentage of tetramer⁺ cells among CD45RA⁻ memory cells. Data for all EOC patients with spontaneous immune responses to ESO (S) are shown in comparison to the frequency (mean ± SD) of ESO tetramer⁺ cells in post-vaccine samples from patients having received a recombinant ESO vaccine (V) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022845#pone.0022845-Ayyoub2" target="_blank">[17]</a>. <b>B</b>. Dot plots show the expression of CD25 and CD127 in total memory cells and in tetramer⁺ cells of one EOC patient. Data corresponding to the proportion of conventional, CD25⁻CD127⁺ and CD25⁻CD127⁻, and Treg, CD25⁺CD127⁻, populations within tetramer⁺ cells for all EOC patients (S) are summarized and compared to the proportion (mean ± SD) of these populations in vaccine-induced tetramer⁺ cells (V). <b>C</b>. Dot plots show the expression of CCR7 and CD27 in total memory cells and in tetramer⁺ cells of one EOC patient. Data corresponding to the proportion of CCR7⁺, CCR7⁻CD27⁺ and CCR7⁻CD27⁻ populations within tetramer⁺ cells for all EOC patients (S) are summarized and compared to the proportion (mean ± SD) of these populations in vaccine-induced tetramer⁺ cells (V). Statistical analyses were performed using a standard two-tailed <i>t</i>-test.</p