Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma.
AuthorsWeed DT, Vella JL, Reis IM, De la Fuente AC, Gomez C, Sargi Z, Nazarian R, Califano J, Borrello I, Serafini P,
Journal
PubMed ID25320361
Myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) play a key role in the progression of head and neck squamous cell carcinoma (HNSCC). On the basis of our preclinical data demonstrating that phosphodiesterase-5 (PDE5) inhibition can modulate these cell populations, we evaluated whether the PDE5 inhibitor tadalafil can revert ... More
Influenza A and methicillin-resistant Staphylococcus aureus co-infection in rhesus macaques - A model of severe pneumonia.
'Influenza results in up to 500,000 deaths annually. Seasonal influenza vaccines have an estimated 60% effectiveness, but provide little or no protection against novel subtypes, and may be less protective in high-risk groups. Neuraminidase inhibitors are recommended for the treatment of severe influenza infection, but are not proven to reduce ... More
Treatment with retinoid X receptor agonist IRX4204 ameliorates experimental autoimmune encephalomyelitis.
AuthorsChandraratna RA, Noelle RJ, Nowak EC,
JournalAm J Transl Res
PubMed ID27158387
'Retinoid x receptors (RXRs) are master regulators that control cell growth, differentiation, and survival and form heterodimers with many other family members. Here we show that treatment with the RXR agonist IRX4204 enhances the differentiation of CD4(+) T cells into inducible regulatory T cells (iTreg) and suppresses the development of ... More
A tractable, simplified ex vivo human skin model of wound infection.
AuthorsYoon DJ, Fregoso DR, Nguyen D, Chen V, Strbo N, Fuentes JJ, Tomic-Canic M, Crawford R, Pastar I, Isseroff RR,
JournalWound Repair Regen
PubMed ID30825247
'The prevalence of infection in chronic wounds is well documented in the literature but not optimally studied due to the drawbacks of current methodologies. Here, we describe a tractable and simplified ex vivo human skin model of infection that addresses the critical drawbacks of high costs and limited translatability. Wounds ... More
Targeting Hypoxia-Induced Carbonic Anhydrase IX Enhances Immune-Checkpoint Blockade Locally and Systemically.
AuthorsChafe SC, McDonald PC, Saberi S, Nemirovsky O, Venkateswaran G, Burugu S, Gao D, Delaidelli A, Kyle AH, Baker JHE, Gillespie JA, Bashashati A, Minchinton AI, Zhou Y, Shah SP, Dedhar S,
JournalCancer Immunol Res
PubMed ID31088846
'Treatment strategies involving immune-checkpoint blockade (ICB) have significantly improved survival for a subset of patients across a broad spectrum of advanced solid cancers. Despite this, considerable room for improving response rates remains. The tumor microenvironment (TME) is a hurdle to immune function, as the altered metabolism-related acidic microenvironment of solid ... More
Sex-associated TSLP-induced immune alterations following early-life RSV infection leads to enhanced allergic disease.
'Many studies have linked severe RSV infection during early-life with an enhanced likelihood of developing childhood asthma, showing a greater susceptibility in boys. Our studies show that early-life RSV infection leads to differential long-term effects based upon the sex of the neonate; leaving male mice prone to exacerbation upon secondary ... More
Crizotinib-induced immunogenic cell death in non-small cell lung cancer.
AuthorsLiu P, Zhao L, Pol J, Levesque S, Petrazzuolo A, Pfirschke C, Engblom C, Rickelt S, Yamazaki T, Iribarren K, Senovilla L, Bezu L, Vacchelli E, Sica V, Melis A, Martin T, Xia L, Yang H, Li Q, Chen J, Durand S, Aprahamian F, Lefevre D, Broutin S, Paci A, Bongers A, Minard-Colin V, Tartour E, Zitvogel L, Apetoh L, Ma Y, Pittet MJ, Kepp O, Kroemer G,
JournalNat Commun
PubMed ID30940805
'Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulates antitumor immune responses. Here we unravel the results of an unbiased screen identifying high-dose (10?µM) crizotinib as an ICD-inducing tyrosine kinase inhibitor that has exceptional antineoplastic activity when combined with non-ICD inducing chemotherapeutics like cisplatin. The ... More
Mannose-Capped Lipoarabinomannan from Mycobacterium tuberculosis Induces CD4+ T Cell Anergy via GRAIL.
AuthorsSande OJ, Karim AF, Li Q, Ding X, Harding CV, Rojas RE, Boom WH,
JournalJ Immunol
PubMed ID26667170
Mycobacterium tuberculosis cell wall glycolipid, lipoarabinomannan, can inhibit CD4(+) T cell activation by downregulating the phosphorylation of key proximal TCR signaling molecules: Lck, CD3?, ZAP70, and LAT. Inhibition of proximal TCR signaling can result in T cell anergy, in which T cells are inactivated following an Ag encounter, yet remain ... More
Vagal Regulation of Group 3 Innate Lymphoid Cells and the Immunoresolvent PCTR1 Controls Infection Resolution.
Uncovering mechanisms that control immune responses in the resolution of bacterial infections is critical for the development of new therapeutic strategies that resolve infectious inflammation without unwanted side effects. We found that disruption of the vagal system in mice delayed resolution of Escherichia coli infection. Dissection of the right vagus ... More
A2AR Adenosine Signaling Suppresses Natural Killer Cell Maturation in the Tumor Microenvironment.
AuthorsYoung A, Ngiow SF, Gao Y, Patch AM, Barkauskas DS, Messaoudene M, Lin G, Coudert JD, Stannard KA, Zitvogel L, Degli-Esposti MA, Vivier E, Waddell N, Linden J, Huntington ND, Souza-Fonseca-Guimaraes F, Smyth MJ,
JournalCancer Res
PubMed ID29229601
Extracellular adenosine is a key immunosuppressive metabolite that restricts activation of cytotoxic lymphocytes and impairs antitumor immune responses. Here, we show that engagement of A2A adenosine receptor (A2AR) acts as a checkpoint that limits the maturation of natural killer (NK) cells. Both global and NK-cell-specific conditional deletion of A2AR enhanced ... More
Generation of human iPSCs from fetal prostate fibroblasts HPrF.
Human induced pluripotent stem cell line was generated from commercially available primary human prostate fibroblasts HPrF derived from a fetus, aged 18-24?weeks of gestation. The fibroblast cell line was reprogrammed with Yamanaka factors (OCT4, SOX2, c-MYC, KLF4) using CytoTune™-iPS 2.0 Sendai Reprogramming Kit. Pluripotency of the derived transgene-free iPS cell ... More
Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells.
AuthorsDajon M, Iribarren K, Petitprez F, Marmier S, Lupo A, Gillard M, Ouakrim H, Victor N, Vincenzo DB, Joubert PE, Kepp O, Kroemer G, Alifano M, Damotte D, Cremer I,
JournalOncoimmunology
PubMed ID30546943
In non-small cell lung carcinoma (NSCLC), stimulation of toll-like receptor 7 (TLR7), a receptor for single stranded RNA, is linked to tumor progression and resistance to anticancer chemotherapy. However, the mechanism of this effect has been elusive. Here, using a murine model of lung adenocarcinoma, we demonstrate a key role ... More
Peripheral T cell cytotoxicity predicts T cell function in the tumor microenvironment.
AuthorsIwahori K, Shintani Y, Funaki S, Yamamoto Y, Matsumoto M, Yoshida T, Morimoto-Okazawa A, Kawashima A, Sato E, Gottschalk S, Okumura M, Kumanogoh A, Wada H,
JournalSci Rep
PubMed ID30796310
Cancer immunotherapy, including immune checkpoint inhibitors, exerts beneficial effects in cancer patients. However, immune checkpoint inhibitors are only advantageous for a limited population of cancer patients. Therefore, companion diagnostics are needed in order to identify patients for whom these therapies are effective. In the present study, we evaluated detailed immunological ... More