Case report: Immune response characterization of a pseudoprogression in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic NSCLC.

A patient with a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic non-small cell lung cancer (NSCLC) experienced a multisite radiological progression at 3 months after initiation of chemoimmunotherapy as first-line treatment for metastatic disease. After the radiological progression, while she was not undergoing treatment, the patient had spontaneous lesions shrinkage and further achieved a prolonged complete response. Genomic and transcriptomic data collected at baseline and at the time of pseudoprogression allowed us to biologically characterize this rare response pattern. We observed the presence of a tumor-specific T-cell response against tumor-specific neoantigens (TNAs). Endogenous retroviruses (ERVs) expression following chemoimmunotherapy was also observed, concurrent with biological features of an anti-viral-like innate immune response with type I IFN signaling and production of CXCR3-associated chemokines. This is the first biological characterization of a NSCLC pseudoprogression under chemoimmunotherapy followed by a prolonged complete response in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated NSCLC. These clinical and biological data underline that even patients with multiple factors of resistance to immune checkpoint inhibitors could trigger a tumor-specific immune response to tumor neoantigen, leading to complete eradication of the tumor and probably a vaccinal immune response.

Custom multi­tumor next­generation sequencing panel for routine molecular diagnosis of solid tumors: Validation and results from three­year clinical use.

Molecular testing is extremely important in cancer care, starting as early as at diagnosis. In order to address the challenge of providing reliable results within the timeframe adapted to patient management and suitable to guide clinical decisions, a capture­based next­generation sequencing (NGS) panel focusing on ten genes known to harbor genetic variations which may be targeted by approved drugs in patients with cancer was designed and validated. Very favorable analytical performances were obtained for both solid and liquid biopsies. For solid biopsies, a low read depth (80X per nucleotide) led to the genotype detection accuracy of 100%. The read of raw data for liquid biopsies resulted in the 91.19% result concordance between paired solid and liquid samples. The present method met all the requirements for the ISO15189 certification. During our three­year experience of routinely using this panel, almost 2,300 samples from lung and colorectal cancers, melanomas and gastrointestinal stromal tumors have been analyzed. It was found that our panel detected slightly more gain­of­function variants than described in the literature. Surprisingly, loss­of­function variants were also detected in certain of the analyzed genes. Finally, liquid biopsy data revealed statistically different mutated allele frequencies between tumor types, but also between mutated genes and variants themselves. In conclusion, the use of our capture­based NGS panel is perfectly adapted to perform relevant molecular diagnosis in a time frame compatible with patient care.

Epidemiological characteristics and clinical outcomes of human rhinovirus infections in a hospitalized population. Severity is independently linked to RSV coinfection and comorbidities.

Human rhinovirus (hRV) is a predominant respiratory viral pathogen. The determinants that lead to adverse clinical outcomes in hospitalized patients are unclear. Our objective was to analyze the epidemiological and clinical characteristics of hRV infections in a hospitalized population and to compare non-severe and severe infections. The study was based on data from all patients with a respiratory episode admitted to Hospital from October 2015 to September 2016. During the study period, out of 2465 respiratory episodes, 434 were detected positive for hRV. Most of the coinfections involved the respiratory syncytial virus (RSV) and very few influenza viruses. A possible interference between rhinovirus and influenza virus is suggested. Airway involvement was present in a large part of hRV infections with 28.4 % (n = 48/169) of bronchiolitis and 3.6 % (n = 6/169) of bronchitis. One third of patients had at least one of the following severity criteria: need for oxygen therapy, hospitalization ≥ 5 days, and admission to the ICU. On multivariate analysis, a respiratory co-infection with RSV and the presence of a chronic respiratory disease (including a history of asthma) were shown to be independent risk factors for the onset of a severe infection in patients ≤ 2 years old. In a case control study based on 70 patients, hRV-A was the predominant lineage, followed closely by hRV-C. High viral load or viral genotypes were not associated with severe infection.