Publications by authors named "Validire P"

Background And Objective: Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status.

Methods: A prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up.

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On one hand, regulatory T cells (Tregs) play an immunosuppressive activity in most solid tumors but not all. On the other hand, the organization of tumor-infiltrating immune cells into tertiary lymphoid structures (TLS) is associated with long-term survival in most cancers. Here, we investigated the role of Tregs in the context of Non-Small Cell Lung Cancer (NSCLC)-associated TLS.

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The complement system plays a complex role in cancer. In clear cell renal cell carcinoma (ccRCC), local production of complement proteins drives tumor progression, but the mechanisms by which they do this are poorly understood. We found that complement activation, as reflected by high plasma C4d or as C4d deposits at the tumor site, was associated with poor prognosis in two cohorts of patients with ccRCC.

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The complement system is a powerful and druggable innate immune component of the tumor microenvironment. Nevertheless, it is challenging to elucidate the exact mechanisms by which complement affects tumor growth. In this study, we examined the processes by which the master complement regulator factor H (FH) affects clear cell renal cell carcinoma (ccRCC) and lung cancer, two cancers in which complement overactivation predicts poor prognosis.

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Article Synopsis
  • * This study analyzed 56 NSCLC patients and found that high densities of TLS-B cells correlated with better profiles of CD4 T cells, showing more naïve and activated types while reducing regulatory T cells (Tregs) and immune checkpoints.
  • * A larger study involving 538 untreated NSCLC patients indicated that high TLS-B cell density could mitigate negative impacts from high Treg levels, with patients exhibiting both high TLS-B and Treg densities showing the best survival rates, highlighting B cells' crucial role in immune protection.
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Accumulation of CD103CD8 resident memory T (T) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of T to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multiplex immunofluorescence on cohorts of non-small cell lung cancer patients treated with anti-PD-(L)1, we show that an increased density of CD103CD8 lymphocytes in immunotherapy-naive tumors is associated with greatly improved outcomes.

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  • NK cells in tumors are crucial for fighting cancer, but they can become dysfunctional in the tumor microenvironment (TME) due to inhibitory molecules.
  • The study analyzed gene expression in NK cells from human lung tumors and non-tumorous lung tissue to understand their inhibitory functions.
  • Findings revealed a specific gene signature indicating NK cell dysfunction in non-small cell lung carcinoma (NSCLC) and highlighted the role of certain receptors and proteins in impacting their effectiveness against tumors.
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Thoracic endometriosis (TE) syndrome is a clinical condition known as an extrapelvic form of endometriosis with the presence of functioning endometrial tissue involving lung parenchyma, pleura, chest wall, or diaphragm. In an effort to obtain an endometriosis ex vivo model, we established the spontaneously growing TH-EM1 cell line from endometriotic implants in lung parenchyma from a woman with TE. Maintained in long-term culture, the cells grew as large mesenchymal-like cells with a doubling time between 5 and 6 days.

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Purpose: The aim of this study was to investigate the association between expression of insulin-like growth factor-1 receptor (IGF1R) and its ligand, IGF-II, and disease-free survival (DFS) in patients with stage III colon cancer (CC).

Methods: In this retrospective study we included consecutive patients who underwent curative surgery for stage III CC. IGF1R and IGF-II/IGF2 status were evaluated in tumour samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR).

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Thymomas are associated with a very high risk of developing Myasthenia Gravis (MG). Our objectives were to identify histological and biological parameters to allow early diagnosis of thymoma patients susceptible to developing MG. We conducted a detailed retrospective analysis from a patient database, searching for differences between patients with thymoma-associated MG (MGT, n = 409) and thymoma without MG (TOMA, n = 111) in comparison with nonthymomatous MG patients (MG, n = 1246).

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Neuropilin-1 (Nrp-1) is a marker for murine CD4FoxP3 regulatory T (Treg) cells, a subset of human CD4 Treg cells, and a population of CD8 T cells infiltrating certain solid tumours. However, whether Nrp-1 regulates tumour-specific CD8 T-cell responses is still unclear. Here we show that Nrp-1 defines a subset of CD8 T cells displaying PD-1 status and infiltrating human lung cancer.

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Clear-cell renal cell carcinoma (ccRCC) possesses an unmet medical need, particularly at the metastatic stage, when surgery is ineffective. Complement is a key factor in tissue inflammation, favoring cancer progression through the production of complement component 5a (C5a). However, the activation pathways that generate C5a in tumors remain obscure.

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Thoracic endometriosis (TE) syndrome is a clinical condition known as an extrapelvic form of endometriosis with the presence of functioning endometrial tissue involving lung parenchyma, pleura, chest wall, or diaphragm. In an effort to obtain an endometriosis ex vivo model, we established the spontaneously growing TH-EM1 cell line from endometriotic implants in lung parenchyma from a woman with TE. Maintained in long-term culture, the cells grew as large mesenchymal-like cells with a doubling time between 5 and 6 days.

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Tumours often evade CD8 T-cell immunity by downregulating TAP. T-cell epitopes associated with impaired peptide processing are immunogenic non-mutated neoantigens that emerge during tumour immune evasion. The preprocalcitonin (ppCT) neoepitope belongs to this category of antigens.

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The highly complex and heterogenous ecosystem of a tumour not only contains malignant cells, but also interacting cells from the host such as endothelial cells, stromal fibroblasts, and a variety of immune cells that control tumour growth and invasion. It is well established that anti-tumour immunity is a critical hurdle that must be overcome for tumours to initiate, grow and spread and that anti-tumour immunity can be modulated using current immunotherapies to achieve meaningful anti-tumour clinical responses. Pioneering studies in melanoma, ovarian and colorectal cancer have demonstrated that certain features of the tumour immune microenvironment (TME)-in particular, the degree of tumour infiltration by cytotoxic T cells-can predict a patient's clinical outcome.

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Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high. Improvements to patient selection and identification of at-risk patients are central to reducing mortality. We aimed to determine if cancer aggressiveness correlates with androgen levels in patients undergoing radical prostatectomy for localized PCa.

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Introduction: Probe-based confocal laser endomicroscopy (pCLE) is an innovative technique providing real-time, in vivo optical biopsies. A previous ex vivo phase of the study (PERSEE) allowed identifying accurate pCLE criteria for the diagnosis of hepatic and peritoneal surgical specimens. This study aimed at evaluating the pCLE role for in vivo intra-abdominal tissue characterization during digestive cancer surgical procedures.

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Co-stimulatory and inhibitory receptors expressed by immune cells in the tumor microenvironment modulate the immune response and cancer progression. Their expression and regulation are still not fully characterized and a better understanding of these mechanisms is needed to improve current immunotherapies. Our previous work has identified a novel ligand/receptor pair, LLT1/CD161, that modulates immune responses.

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Chronic obstructive pulmonary disease (COPD) is a highly prevalent and devastating condition for which no curative treatment is available. Exaggerated lung cell senescence may be a major pathogenic factor. Here, we investigated the potential role for mTOR signaling in lung cell senescence and alterations in COPD using lung tissue and derived cultured cells from patients with COPD and from age- and sex-matched control smokers.

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Article Synopsis
  • SOX8 is a transcription factor involved in sex determination, and while its role in humans isn't fully understood, it is expressed in early gonadal development.
  • Research identified SOX8 mutations and chromosomal rearrangements in individuals with 46, XY disorders of sex development (DSD) and male infertility, suggesting a link to reproductive issues.
  • SOX8 mutations were found more frequently in infertile men and women with primary ovarian insufficiency, indicating that alterations in SOX8's function could contribute to various reproductive conditions.
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  • A new device was assessed for its ability to analyze breast masses using label-free fluorescence spectral analysis on freshly removed surgical samples.
  • The study involved 64 breast masses, where results showed that maximum fluorescence intensity effectively distinguished between benign and malignant tumors with a significant p-value, and optimal data collection suggested taking five random measurements for best accuracy.
  • The device achieved high sensitivity (98.8%) and strong negative predictive values (97.2%), indicating it can accurately differentiate breast mass types and is suitable for further clinical development.
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  • CD8/CD103 tissue-resident memory T cells in solid tumors are linked to better outcomes, but the function of CD103 in these T cells is not well understood.
  • The study investigates the role of CD103 and its interaction with a protein called paxillin (Pxn) in T cell function and signaling when they bind to E-cadherin in the tumor environment.
  • Findings reveal that paxillin is crucial for T cell adhesion and function; inhibiting its activation impairs tumor-targeting abilities of T cells, highlighting why their presence in tumors correlates with improved prognosis.
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Natural Killer (NK) cells control metastatic dissemination of murine tumors and are an important prognostic factor in several human malignancies. However, tumor cells hijack many of the NK cell functional features compromising their tumoricidal activity. Here, we show a deleterious role of the TNFα/TNFR2/BIRC3/TRAF1 signaling cascade in NK cells from the tumor microenvironment (TME).

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