Differences of tumor-recruiting myeloid cells in murine squamous cell carcinoma influence the efficacy of immunotherapy combined with a TLR7 agonist and PD-L1 blockade

Publication date: April 2019

Source: Oral Oncology, Volume 91

Author(s): Hidetake Tachinami, Naoto Nishii, Yulong Xia, Yoshihisa Kashima, Tatsukuni Ohno, Shigenori Nagai, Lixin Li, Walter Lau, Kei Tomihara, Makoto Noguchi, Miyuki Azuma

Abstract

Objectives

The immune status of the tumor microenvironment has a marked impact on clinical outcomes. Here we examined the immune environments of tumor-infiltrating leukocytes (TILes) in two murine models of squamous cell carcinoma and compared the effects of immunotherapeutic agents, including a TLR7 agonist and an immune checkpoint inhibitor, and a chemotherapeutic agent, gemcitabine, in these models.

Materials and methods

TILes from NR-S1- and SCCVII-grafted mice were analyzed by flow cytometry. NR-S1-inoculated mice received resiquimod (a synthetic TLR7 agonist), an anti-PD-L1 antibody, or both, and tumor growth and TILs were examined. Gemcitabine was administered to deplete CD11b⁺ cells.

Results

More than 50% of TILes from NR-S1- and SCCVII-inoculated mice were CD11b⁺Gr-1⁺ cells. A major fraction of NR-S1 CD11b⁺ cells was Ly6G^highLy6C^low-negaF4/80⁻ tumor-associated neutrophils (TANs) and the majority of SCCVII CD11b⁺ cells were Ly6G^lowLy6C⁻F4/80⁺ tumor-associated macrophages. NR-S1 TANs did not express MHC class II and CD86, but did express reactive oxygen species and PD-L1. Resiquimod, alone and in combination with an anti-PD-L1 antibody, did not regress NR-S1 tumors, but the combination increased the CD8/regulatory T cell-ratio, and IFN-γ and PD-1 expression in CD8⁺ TILes. Pre-administration of low-dose gemcitabine prior to the combination treatment suppressed the progression of NR-S1 tumors.

Conclusions

NR-S1 tumors with abundant recruitment of TANs were resistant to treatments with a TLR7 agonist, alone and in combination with PD-1 blockade, and required an additional gemcitabine treatment. The phenotype and status of tumor-infiltrating CD11b⁺ myeloid cells may influence the efficacy of immunotherapeutic agents.

https://ift.tt/2U1sMB1

B cell-intrinsic requirement for STK4 in humoral immunity in mice and humans

Publication date: Available online 20 February 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Imogen Moran, Danielle T. Avery, Kathryn Payne, Helen Lenthall, E.Graham Davies, Siobhan Burns, Winnie Ip, Matÿfffedas M. Oleastro, Ismail Reisli, Sukru Guner, Sevgi Keles, Luigi Notarangelo, Elissa K. Deenick, Christopher C. Goodnow, David Zahra, Robert Brink, CIRCA, Melanie Wong, Stuart G. Tangye, Cindy S. Ma, Tri Giang Phan

https://ift.tt/2U6pigZ

Lymphoproliferative Disease in Wiskott-Aldrich Syndrome. Analysis of the French Registry of Primary Immunodeficiencies

Publication date: Available online 20 February 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Morgane Cheminant, Nizar Mahlaoui, Céline Desconclois, Danielle Canioni, Loïc Ysebaert, Loïc Dupré, Zilton Vasconcelos, Marion Malphettes, Despina Moshous, Bénédicte Neven, Pierre-Simon Rohrlich, Marc Bernard, Yves Bertrand, Alain Fischer, Felipe Suarez

https://ift.tt/2BMgaqx

NR Supplementation During Lactation: Benefiting Mother and Child

Publication date: Available online 21 February 2019

Source: Trends in Endocrinology & Metabolism

Author(s): Dengbao Yang, Yihong Wan

Abnormal nicotinamide adenine dinucleotide (NAD⁺) metabolism causes a wide spectrum of diseases. A recent study (Cell Rep. 2019;26:969–983) shows that postpartum NAD⁺ homeostasis is depressed. By restoring NAD⁺ homeostasis, maternal nicotinamide riboside (NR) supplementation during lactation enhances postpartum weight loss, as well as juvenile development and adult neurogenesis in the offspring.

https://ift.tt/2EkZtnV

CO2 Laser Supraglottic Resurfacing for Non-Granulomatous Chronic Supraglottitis in Two Children

Publication date: Available online 20 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Matthew M. Smith, Johanna Nokso-Koivisto, Brittany A. Leader, Lyndy J. Wilcox, Michael J. Rutter

Abstract

Chronic epiglottitis and supraglottitis are clinical entities that present with respiratory distress and are primarily associated with autoimmune disorders, gastroesophageal reflux disease, or angioedema. First described in adults with sarcoidosis in 2010, CO2 laser epiglottis resurfacing has been effective in reducing epiglottic edema. We present two cases of adolescent males with non-granulomatous chronic supraglottitis who were successfully treated with CO2 laser supraglottic resurfacing.

https://ift.tt/2X8J11c

Title: Tertiary Hospital Retrospective Observational Audit of Tonsillectomy

Publication date: Available online 20 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Hannah Ng, Eugene Wong, John Curotta, Susan Trapani, Alan T. Cheng

Abstract

Objectives

Tertiary hospitals see a wide array of complex paediatric patients requiring the procedure of tonsillectomy to alleviate airway symptoms. To investigate the implications of patient-specific factors on postoperative morbidities and hospital stay length, including the role of BMI and AH as predictors for airway complications following surgery.

Methods

A retrospective chart review was performed for all patients presenting at The Children's Hospital at Westmead for routine tonsillectomy between July 2010 and July 2014.

Results

Of 500 charts, 420 patients met inclusion criteria. 155 (37%) patients had a pre-existing comorbidity. Polysomnogram (PSG) was conducted prior to surgery (n=129). BMI results showed a mean BMI of 20.0, n=25 were overweight, n=70 were obese and n=11 underweight. 84 patients (20%) experienced a postoperative complication/unexpected morbidity. There were no returns to theatre and no mortality. 24 patients had more than one complication. Complication rate was highest in the patients <2 years of age. There was a statistically significant difference in the number of desaturation related complications between obese and non-obese groups p=0.00480. There was statistically significant difference in length of hospital stay between the two groups. 16% of children with co-morbidities stayed for >2 nights in hospital (25/155) compared to 7.5% of children without co-morbidities p=0.00607. 9% of children with co-morbidities stayed for 3 nights in hospital (14/155) compared to patients without co-morbidities (6/256), p= 0.00167.

Conclusions

This audit confirms the impact of age, obesity and certain co-morbidities on the potential costs to the hospital in managing complications and length of stay after surgery.

https://ift.tt/2SgFF8D

Prevention of upper aerodigestive tract cancer through active search strategies and use of equipped propaedeutics

Publication date: Available online 20 February 2019

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Francis Balduino Guimarães Santos, Fernando Danelon Leonhardt, Márcio Abrahão

Abstract

Introduction

Upper aerodigestive tract cancer is among the most frequent malignancies and has epidemiological importance worldwide. Most cases are already advanced at the diagnosis, with a strong negative impact on survival and high cost to the government. Campaigns directed against these cancers have often failed in Brazil.

Objective

To evaluate the effectiveness of screening for upper aerodigestive tract cancers, using active search strategies and the use of equipped propaedeutics.

Methods

A cross-sectional, prospective, descriptive, analytical and exploratory study, since its objectives are based on the visualization of cancerous lesions in a sample consisting of individuals with risk factors, aiming to expand the necessary knowledge for cancer detection, aiming at secondary prevention of the oral cavity, oropharynx, larynx and hypopharynx cancer.

Results

A total of 16.7% of precancerous lesions and 0.5% of cancer lesions located in the upper aerodigestive tract were clinically visualized.

Conclusion

The method was effective in the identification of precancerous lesions for the purpose of secondary prevention, but equally important against upper aerodigestive tract cancer, since in the present study the chance of finding the latter was increased by 22.7, showing it is an alternative for future campaigns against the disease.

Resumo

Introdução

O câncer do trato aerodigestivo superior configura-se entre os mais frequentes e apresenta-se com importância epidemiológica no mundo. A maior parte apresenta-se avançada ao diagnóstico, com forte impacto negativo na sobrevida e elevado custo ao erário. As campanhas realizadas contra esses cânceres têm frequentemente falhado no Brasil.

Objetivo

Avaliar a efetividade do rastreamento para lesões cancerizáveis do trato aerodigestivo superior, usando-se estratégias de busca ativa e uso da propedêutica armada.

Método

Estudo transversal, prospectivo, descritivo, analítico e exploratório, uma vez que os seus objetivos se alicerçam na visualização das lesões cancerizáveis numa amostra composta por indivíduos com fatores de risco, de forma a aprofundar o conhecimento necessário para a sua detecção, visando à prevenção secundária do câncer da cavidade oral, orofaringe, laringe e hipofaringe.

Resultado

Foram visualizadas clinicamente 16,7% lesões cancerizáveis e 0,5% cânceres de localização no trato aerodigestivo superior.

Conclusão

O método mostrou-se efetivo na identificação de lesões cancerizáveis com intuito de prevenção secundária, mas igualmente importante contra o câncer do trato aerodigestivo superior, uma vez que neste presente estudo multiplicou-se a chance do encontro deste por 22,7; apresentando-se como alternativa para futuras campanhas contra a doença.

https://ift.tt/2NimN8C