Menée in vitro et à l'aide de souris transgéniques, cette étude identifie les mécanismes par lesquels le virus HTLV-1 peut persister dans l'organisme malgré une forte réponse immunitaire et favoriser le développement d'une leucémie-lymphome à cellules T de l'adulte

HTLV-1 persistence and the oncogenesis of adult T cell leukemia/lymphoma

Bangham, Charles R M

Human T-cell leukemia virus type 1 (HTLV-1), also known as human T-lymphotropic virus type 1, causes the aggressive malignancy known as adult T-cell leukemia/lymphoma (ATL) in 5% of infected people, and a chronic progressive inflammatory disease of the central nervous system - HTLV-1-associated myelopathy (HAM) - in a further 0.3% to 4%, varying between endemic regions. Reliable treatments are lacking for both conditions, although there have been promising recent advances in the prevention and [...]

Menée in vitro et à l'aide de xénogreffes sur des modèles murins, cette étude identifie un mécanisme par lequel la kinase AMPK, en phosphorylant et stabilisant le transporteur de cuivre CTR1, favorise la carcinogenèse mammaire et met en évidence l'intérêt d'utiliser des chélateurs du cuivre lors d'un traitement utilisant des agonistes de la kinase AMPK

AMPK phosphorylates and stabilises copper transporter 1 to synergise metformin and copper chelator for breast cancer therapy

Zhang, Xiaomei ; Jiang, Qiwei ; Su, Yaqing ; Bu, Lang ; Sun, Zicheng ; Wu, Xueji ; Gao, Bing ; Wang, Lei ; Lin, Ying ; Xie, Wei ; Guo, Jianping

Background : Predominant roles of copper and its transporter, copper transporter 1 (CTR1), in tumorigenesis have been explored recently; however, the upstream regulation of CTR1 and combinational intervention of copper chelators in malignancies remain largely unclear. Methods : CRISPR/Cas9-based kinome screening was used to identify the CTR1 upstream kinases. Immunofluorescence assays were utilised to detect CTR1 localisation. In vitro kinase assays and mass spectrometry were performed to [...]

Menée à partir de données portant sur des échantillons cervicaux de femmes présentant ou non une infection par le papillomavirus humain (HPV), cette étude examine les changements induits par le HPV au niveau de l'épigénome avant le développement d'anomalies cytologiques

HPV-induced host epigenetic reprogramming is lost upon progression to high-grade cervical intraepithelial neoplasia

Herzog, Chiara ; Vavourakis, Charlotte D. ; Barrett, James E. ; Karbon, Gerlinde ; Villunger, Andreas ; Wang, Jiangrong ; Sundström, Karin ; Dillner, Joakim ; Widschwendter, Martin

The impact of a pathogen on host disease can only be studied in samples covering the entire spectrum of pathogenesis. Persistent oncogenic Human Papilloma Virus (HPV) infection is the most common cause for cervical cancer. Here, we investigate HPV-induced host epigenome-wide changes prior to development of cytological abnormalities. Using cervical sample methylation array data from disease-free women with or without an oncogenic HPV infection, we develop the WID (Women's cancer risk [...]

Cet article analyse les mécanismes par lesquels les cellules cancéreuses stimulent la formation par les neutrophiles de pièges extracellulaires, examine comment ces pièges favorisent la progression tumorale et augmentent le risque de décès par événements cardiovasculaires puis propose des stratégies thérapeutiques permettant de cibler les pièges extracellulaires

NETworking with cancer: The bidirectional interplay between cancer and neutrophil extracellular traps

Adrover, Jose M. ; McDowell, Sheri A. C. ; He, Xue-Yan ; Quail, Daniela F. ; Egeblad, Mikala

Neutrophils are major effectors and regulators of the immune system. They play critical roles not only in the eradication of pathogens but also in cancer initiation and progression. Conversely, the presence of cancer affects neutrophil activity, maturation, and lifespan. By promoting or repressing key neutrophil functions, cancer cells co-opt neutrophil biology to their advantage. This co-opting includes hijacking one of neutrophils? most striking pathogen defense mechanisms: the formation of [...]

Cet article passe en revue les facteurs contribuant au déclin des cellules souches hématopoïétiques au cours du vieillissement puis identifie les stratégies pouvant permettre de maintenir la fonction de ces cellules et de prévenir ou de retarder la survenue d'hémopathies malignes

Hematopoietic Stem Cell Aging and Leukemia Transformation

Colom Díaz, Patricia A. ; Mistry, Jayna J. ; Trowbridge, Jennifer J.

With aging, hematopoietic stem cells (HSCs) have an impaired ability to regenerate, differentiate, and produce the entire repertoire of mature blood and immune cells. Due to dysfunctional hematopoiesis, the incidence of hematologic malignancies increases in elderly individuals. Here, we provide an update on HSC-intrinsic and HSC-extrinsic factors and processes recently discovered to contribute to functional decline of HSCs during aging. In addition, we discuss targets and timing of intervention [...]

Cet article analyse les données concernant le rôle des macro- et micro-environnements tumoraux dans la cachexie liée au cancer puis passe en revue les nouvelles stratégies pour traiter ce syndrome

Cancer-associated cachexia — understanding the tumour macroenvironment and microenvironment to improve management

Argilés, Josep M. ; López-Soriano, Francisco J. ; Stemmler, Britta ; Busquets, Sílvia

Cachexia is a devastating, multifactorial and often irreversible systemic syndrome characterized by substantial weight loss (mainly of skeletal muscle and adipose tissue) that occurs in around 50–80% of patients with cancer. Although this condition mainly affects skeletal muscle (which accounts for approximately 40% of total body weight), cachexia is a multi-organ syndrome that also involves white and brown adipose tissue, and organs including the bones, brain, liver, gut and heart. Notably, [...]

Cet article compare les mécanismes de formation et de régulation des veinules à endothélium épais (HEVs) dans les ganglions lymphatiques et les tumeurs puis examine le rôle des HEVs tumoraux dans l'immunité antitumorale

High endothelial venules in cancer: Regulation, function, and therapeutic implication

Vella, Gerlanda ; Hua, Yichao ; Bergers, Gabriele

The lack of sufficient intratumoral CD8+ T lymphocytes is a significant obstacle to effective immunotherapy in cancer. High endothelial venules (HEVs) are organ-specific and specialized postcapillary venules uniquely poised to facilitate the transmigration of lymphocytes to lymph nodes (LNs) and other secondary lymphoid organs (SLOs). HEVs can also form in human and murine cancer (tumor HEVs [TU-HEVs]) and contribute to the generation of diffuse T cell-enriched aggregates or tertiary lymphoid [...]

Menée à partir de l'analyse immunohistochimique et génétique d'échantillons tissulaires fixés au formaldéhyde et inclus en paraffine après prélèvement sur des patients atteints d'un lymphome diffus à grandes cellules B, cette étude met en évidence, chez les patients âgés dont le lymphome est positif au virus d'Epstein-Barr, la présence fréquente de mutations au niveau des gènes TET2 et LILRB1

TET2 and LILRB1 mutations are frequent in Epstein–Barr virus-positive diffuse large B-cell lymphoma especially in elderly patients

Cho, Junhun ; Kim, Eojin ; Yoon, Sang Eun ; Kim, Seok Jin ; Kim, Won Seog

Background : Diffuse large B-cell lymphoma (DLBCL) harboring Epstein–Barr virus (EBV) primarily occurs in patients who have underlying immunodeficiency or in elderly patients but is also reported in young, immunocompetent patients. The authors investigated the pathologic differences in EBV-positive DLBCL in these three groups of patients. Methods : In total, 57 patients with EBV-positive DLBCL were included in the study; of these, 16 patients had associated immunodeficiency, 10 were young [...]

Cet article passe en revue les caractéristiques moléculaires, cliniques et pathologiques des cancers du poumon présentant un sous-type moléculaire rare (présence de mutations au niveau du gène HRAS, NRAS, RIT1, ARAF, RAF1 ou MAP2K1 ; présence de fusions de gènes ERBB, LTK ou RASGRF1)

Rare molecular subtypes of lung cancer

Harada, Guilherme ; Yang, Soo-Ryum ; Cocco, Emiliano ; Drilon, Alexander

Oncogenes that occur in ≤5% of non-small-cell lung cancers have been defined as ‘rare’; nonetheless, this frequency can correspond to a substantial number of patients diagnosed annually. Within rare oncogenes, less commonly identified alterations (such as HRAS, NRAS, RIT1, ARAF, RAF1 and MAP2K1 mutations, or ERBB family, LTK and RASGRF1 fusions) can share certain structural or oncogenic features with more commonly recognized alterations (such as KRAS, BRAF, MET and ERBB family mutations, or [...]

Menée à l'aide de lignées cellulaires, de modèles murins et de données de séquençage d'ARNs tumoraux provenant de patientes atteintes d'un cancer du sein triple négatif et non métastatique, cette étude met en évidence le rôle, dans la protection immunitaire locale contre la tumeur et l'efficacité des inhibiteurs de point de contrôle immunitaire, d'une sous-population de lymphocytes T CD8+ intratumoraux présentant un phénotype ressemblant à celui des cellules T résidentes mémoires

Intratumoral CD8+ T cells with a tissue-resident memory phenotype mediate local immunity and immune checkpoint responses in breast cancer

Virassamy, Balaji ; Caramia, Franco ; Savas, Peter ; Sant, Sneha ; Wang, Jianan ; Christo, Susan N. ; Byrne, Ann ; Clarke, Kylie ; Brown, Emmaline ; Teo, Zhi Ling ; von Scheidt, Bianca ; Freestone, David ; Gandolfo, Luke C. ; Weber, Karsten ; Teply-Szymanski, Julia ; Li, Ran ; Luen, Stephen J. ; Denkert, Carsten ; Loibl, Sibylle ; Lucas, Olivia ; Swanton, Charles ; Speed, Terence P. ; Darcy, Phillip K. ; Neeson, Paul J. ; Mackay, Laura K. ; Loi, Sherene

CD8+ tumor-infiltrating lymphocytes with a tissue-resident memory T (TRM) cell phenotype are associated with favorable prognosis in patients with triple-negative breast cancer (TNBC). However, the relative contribution of CD8+ TRM cells to anti-tumor immunity and immune checkpoint blockade efficacy in breast cancer remains unknown. Here, we show that intratumoral CD8+ T cells in murine mammary tumors transcriptionally resemble those from TNBC patients. Phenotypic and transcriptional studies [...]