Sub-lethal radiation enhances anti-tumor immunotherapy in a transgenic mouse model of pancreatic cancer

BACKGROUND: It is not uncommon to observe circulating tumor antigen-specific T lymphocytes in cancer patients despite a lack of significant infiltration and destruction of their tumors. Thus, an important goal for tumor immunotherapy is to identify ways to modulate in vivo anti-tumor immunity to achieve clinical efficacy. We investigate this proposition in a spontaneous mouse tumor model, Rip1-Tag2. METHODS: Experimental therapies were carried out in two distinctive trial designs, intended to either intervene in the explosive growth of small tumors, or regress bulky end-stage tumors. Rip1-Tag2 mice received a single transfer of splenocytes from Tag-specific, CD4(+) T cell receptor transgenic mice, a single sub-lethal radiation, or a combination therapy in which the lymphocyte transfer was preceded by the sub-lethal radiation. Tumor burden, the extent of lymphocyte infiltration into solid tumors and host survival were used to assess the efficacy of these therapeutic approaches. RESULTS: In either intervention or regression, the transfer of Tag-specific T cells alone did not result in significant lymphocyte infiltration into solid tumors, not did it affect tumor growth or host survival. In contrast, the combination therapy resulted in significant reduction in tumor burden, increase in lymphocyte infiltration into solid tumors, and extension of survival. CONCLUSIONS: The results indicate that certain types of solid tumors may be intrinsically resistant to infiltration and destruction by tumor-specific T lymphocytes. Our data suggest that such resistance can be disrupted by sub-lethal radiation. The combinatorial approach presented here merits consideration in the design of clinical trials aimed to achieve T cell-mediated anti-tumor immunity

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Validation of respiratory rate measurements from remote monitoring device in COPD patients

International audienceWith healthcare objectives and budget constraint, remote monitoring of chronic obstructive pulmonary disease (COPD) patients is an important challenge in most European countries. Recent works have shown that it is possible to predict COPD exacerbation based on monitoring of simple parameters, such as the respiratory rate (RR) of the patient in spontaneous ventilation or under non-invasive ventilation. Until now, these devices do not allow a daily automatic data remote transmission,[4] or it is restricted to patients under mechanical ventilation. TeleOx® (SRETT, Boulogne-Billancourt, France), the first oxygen flow rate remote monitoring device, also allows a RR measurement by associating a pressure sensor and a fluidic oscillator flow sensor. A median RR is output every 5 minutes based on time interval between two consecutive respiratory cycles.In this study, we compared the corresponding RR measurements between TeleOx® and the reference polygraph (Nox-T3®, Nox Medical Inc. Reykjavik, Iceland) from COPD patients under nasal oxygen therapy with flow rates between 0.5 and 5.0 litres per minute. Patients without mechanical ventilation and without any other respiratory pathology were eligible to the study if they would undergo a ventilatory polygraph record for other reason

Validation of respiratory rate measurements from remote monitoring device in COPD patients

International audienceWith healthcare objectives and budget constraint, remote monitoring of chronic obstructive pulmonary disease (COPD) patients is an important challenge in most European countries. Recent works have shown that it is possible to predict COPD exacerbation based on monitoring of simple parameters, such as the respiratory rate (RR) of the patient in spontaneous ventilation or under non-invasive ventilation. Until now, these devices do not allow a daily automatic data remote transmission,[4] or it is restricted to patients under mechanical ventilation. TeleOx® (SRETT, Boulogne-Billancourt, France), the first oxygen flow rate remote monitoring device, also allows a RR measurement by associating a pressure sensor and a fluidic oscillator flow sensor. A median RR is output every 5 minutes based on time interval between two consecutive respiratory cycles.In this study, we compared the corresponding RR measurements between TeleOx® and the reference polygraph (Nox-T3®, Nox Medical Inc. Reykjavik, Iceland) from COPD patients under nasal oxygen therapy with flow rates between 0.5 and 5.0 litres per minute. Patients without mechanical ventilation and without any other respiratory pathology were eligible to the study if they would undergo a ventilatory polygraph record for other reason