All in the Levels—Programmed Death‐Ligand 1 Expression as a Biomarker for Immune Checkpoint Inhibitor Response in Patients with Gastrointestinal Cancer

Immune checkpoint inhibitors (ICIs) benefit patients with rare subsets of gastrointestinal (GI) cancer. Significant interest exists to identify predictive biomarkers that may increase the applicability of ICI therapy for these patients. Programmed death ligand 1 (PD‐L1) is one such candidate; however, this biomarker has well‐chronicled limitations. Combined positive score (CPS) ≥1 is the minimum PD‐L1 expression threshold necessary for patients with gastric or gastroesophageal junction (GEJ) cancer to qualify for treatment with pembrolizumab; however, studies suggest that patients with higher CPS scores may derive greater benefit. We present the cases of two patients, both with low tumor mutational burden, microsatellite stable, and CPS ≥70 GI tumors (cholangiocarcinoma and GEJ cancer), who have achieved excellent tumor control with pembrolizumab. We postulate that, by testing for CPS in all patients with GI cancer and identifying a CPS threshold predictive of ICI response, PD‐L1 expression could identify the patiets with GI cancer, in tissue agnostic fashion, who could benefit from ICI therapy.     

Gene Expression Signatures of Contact Lens-Induced Myopia in Guinea Pig Retinal Pigment Epithelium

PurposeTo identify key retinal pigment epithelium (RPE) genes linked to the induction of myopia in guinea pigs.MethodsTo induce myopia, two-week-old pigmented guinea pigs (New Zealand strain, n = 5) wore −10 diopter (D) rigid gas-permeable contact lenses (CLs), for one day; fellow eyes were left without CLs and served as controls. Spherical equivalent refractive errors (SE) and axial length (AL) were measured at baseline and one day after initiation of CL wear. RNA sequencing was applied to RPE collected from both treated and fellow (control) eyes after one day of CL-wear to identify related gene expression changes. Additional RPE-RNA samples from treated and fellow eyes were subjected to quantitative real-time PCR (qRT-PCR) analysis for validation purposes.ResultsThe CLs induced myopia. The change from baseline values in SE was significantly different (P = 0.016), whereas there was no significant difference in the change in AL (P = 0.10). RNA sequencing revealed significant interocular differences in the expression in RPE of 13 genes: eight genes were significantly upregulated in treated eyes relative to their fellows, and five genes, including bone morphogenetic protein 2 (Bmp2), were significantly downregulated. The latter result was also confirmed by qRT-PCR. Additional analysis of differentially expressed genes revealed significant enrichment for bone morphogenetic protein (BMP) and TGF-β signaling pathways.ConclusionsThe results of this RPE gene expression study provide further supporting evidence for an important role of BMP2 in eye growth regulation, here from a guinea pig myopia model.     

Genetically determined lean mass and dietary response

Weight loss attenuates many obesity-related co-morbidities, but is difficult to sustain with dietary change. Dietary adherence, not macronutrient composition, is a better predictor of weight loss. Weight loss-induced endocrine changes promote food intake and increase energy efficiency, contributing to the difficulty with dietary adherence and weight regain. Macronutrient preference is partly genetically determined, suggesting that personalized dietary interventions might be more successful. In this issue, Li et al. report that a genetic risk score comprising the cumulative weighted effects of variants previously associated with increased lean mass is associated with increased satiety and weight loss 6 months after initiating a low- but not a high-fat diet. The effects were attenuated by 2 years. These findings suggest that genetic variants may influence response to specific diet. Further studies are necessary to assess whether genetically determined lean mass is causally associated with dietary response. Significant progress has recently been made in identifying additional genetic determinants of lean mass, which will enable such investigations and potentially inform future nutritional studies.     

Antioxidant Levels at Diagnosis in Childhood Acute Lymphoblastic Leukemia

Objective

To measure serum zinc, selenium, retinol and tocoferol levels at diagnosis of pediatric acute lymphoblastic leukemia (ALL) and to compare it to that of a control population. Correlation was made with episodes of febrile neutropenia during the first 8 wk of therapy.

Methods

Fasting levels of serum zinc, selenium, retinol and tocoferol were measured in 45 children diagnosed with acute lymphoblastic leukemia and in 20 healthy controls.

Results

Lower levels of baseline selenium and tocoferol were noted in patients who developed febrile neutropenia compared to the patients who did not (p?=?0.022 and 0.026 respectively). Serum retinol was also lower in patients who developed sepsis when compared to those who did not.

Conclusions

Supplementation of antioxidants may be considered in clinical trials aiming at reducing infection related morbidity and mortality.