Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGFβ activity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 blockade. Here we coupled the artificial intelligence (AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGFβ pathway activity. Analysis of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution patterns. The digital image analysis approach achieves 74% concordance with the pathologist assessment for tumor-immune phenotypes. The transcriptomic profiling suggests that the TIL score was negatively correlated with TGFβ pathway activation, together with elevated TGFβ signaling activity observed in excluded and desert tumor phenotypes. The present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes: immune desert, immune excluded or immune inflamed. The association between "cold" tumor-immune phenotypes and TGFβ signature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGFβ blockade.

OBJECTIVETo evaluate the treatment of obstructive sleep apnea syndrome (OSAS) in children with congenital micrognathia using mandibular distraction osteogenesis and to discuss the advantages and disadvantages of this approach.

METHODS6 patients (4 males, 2 females) had undergone mandibular distraction osteogenesis, 12 distraction devices were placed through extraoral incision for bilateral distraction. The mean age of treatment was 1 year and 9 months (range 4 months to 9 years). Every patient had been evaluated pre and postoperatively with cephalometry. The period of consolidation was 4 - 11 weeks. The period of follow-up was from 2 to 10 months.

RESULTSThe average distraction distance was 19.2 mm (range 15 to 25 mm). The osteotomy and distraction processes were smooth in all the cases, the osteogenesis was good, without infection and other complications. The posterior airway space was increased from averaged 4.5 mm preoperatively to 10. 1mm after surgery. Five children had normal respiration and sleep restored with naso-pharyngeal airway removal or tracheostomy decannulation. One patient is to receive a planned second stage of distraction with a horizontal vector. The results were stable without relapse during a follow-up period of 2 to 10 months.

CONCLUSIONSApplication of mandibular distraction osteogenesis is an important component and effective in the treatment of OSAS and permits mandibular advancement in the younger child. As more experience is gained with distraction osteogenesis in the treatment of children with OSAS, the role of distraction will become better defined.

Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Micrognathism ; complications ; surgery ; Osteogenesis, Distraction ; methods ; Sleep Apnea, Obstructive ; complications ; surgery