Clinicopathological characteristics and tumor infiltrating immune cells associations of PD-L1 tumor expression in non-small cell lung cancer patients.

AIM: Our study aimed to perform on Moroccan patients' non-small cell lung carcinoma (NSCLC) concerning the relationship between PD-L1 tumor expression, clinicopathological features and tumor infiltrating immune cells (ICs). METHODS: This is a retrospective study (2019 to 2021) conducted on samples from Moroccan patients with NSCLC at the Pathological Anatomy Laboratory of Ibn Rochd University Hospital in Casablanca. Eligible participants for our study had to meet the following predefined criteria: age ≥18 years, histologically confirmed NSCLC, no prior therapeutic interventions, availability of clinical and pathological data, and a usable tumor sample for determining PD-L1 status. Exclusion criteria applied to patients with other types of lung cancer and unusable tumor samples. The evaluation of tumor and immune expression of PD-L1 was performed using immunohistochemistry (IHC), with the 22C3 clone on the Dako Autostainer Link 48 platform. Tumor PD-L1 expression was categorized into 3 levels: TPS <1% (negative expression), TPS 1-49% (low expression), and TPS ≥50% (high expression). ICs infiltrating the tumor expressing PD-L1 were considered positive when more than 1% of positive ICs were present. RESULTS: Among the 316 analyzed samples, 56.6% showed a negative expression of PD-L1, 16.8% displayed a low expression of PD-L1, and 26.6% exhibited a strong expression. Regarding the histological type, among patients with TPS ≥ 50%, 25.8% had adenocarcinoma. Among patients with TPS ≥ 50%, 24.81% were smokers. PD-L1 was also strongly expressed in the lung (28.2%) and bronchi (26.5%). PD-L1 expression (TPS ≥ 50%) was observed in 35.29% of early-stage patients. Concerning tumor cells (TCs), 27.5% of tumors infiltrated by ICs had TPS ≥ 50%. Furthermore, coexpression of PD-L1 on both TCs and ICs infiltrating the tumor was found in 27.8% of tumors. Statistical analysis demonstrated a significant association between tumor PD-L1 expression and smoking status (P=0.019). However, no significant difference was observed between PD-L1 expression and the presence of ICs infiltrating the tumor (P=0.652), as well as the IHC expression of PD-L1 on ICs (P=0.259). CONCLUSION: Our results demonstrate a significant association between PD-L1 expression and smoking status. However, no significant association was observed between PD-L1 expression and the presence of infiltrating ICs, nor with the IHC expression of PD-L1 on ICs. Our data underscore the importance of participating in the study of specific factors influencing PD-L1 expression in patients with NSCLC.

The PTPN22 C1858T (R620W) functional polymorphism in inflammatory bowel disease.

OBJECTIVE: In view of the discrepant data regarding the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 (R620W, 1858C→T) polymorphism and susceptibility to autoimmune diseases including inflammatory bowel diseases (IBD), we investigated whether this functional single-nucleotide polymorphism influences IBD risk in a group of Moroccan patients. RESULTS: This is the first report on the prevalence of PTPN22 (R620W) variant in a Moroccan cohort. No evidence of statistically significant differences was observed when the PTPN22 (R620W) allele and genotype distribution among IBD, Crohn's disease (CD), ulcerative colitis (UC) patients and healthy controls were compared. The frequency of the variant allele in healthy subjects was 1.77% compared to 2.56% in the IBD patients and 1.85% in CD patients. Furthermore, the frequency of this allele was increased in UC patients compared to controls (4.17% vs. 1.77%, OR = 2.42, 95% CI 0.82-7.08; P = 0.09), but the difference was not statistically significant. Our data suggest a lack of association between PTPN22 R620W variant and IBD susceptibility in Moroccan patients.

Activation of MITF by Argan Oil Leads to the Inhibition of the Tyrosinase and Dopachrome Tautomerase Expressions in B16 Murine Melanoma Cells.

Argan (Argania spinosa L.) oil has been used for centuries in Morocco as cosmetic oil to maintain a fair complexion and to cure skin pimples and chicken pox pustules scars. Although it is popular, the scientific basis for its effect on the skin has not yet been established. Here, the melanogenesis regulatory effect of argan oil was evaluated using B16 murine melanoma cells. Results of melanin assay using B16 cells treated with different concentrations of argan oil showed a dose-dependent decrease in melanin content. Western blot results showed that the expression levels of tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (DCT) proteins were decreased. In addition, there was an increase in the activation of MITF and ERK1/2. Real-time PCR results revealed a downregulation of Tyr, Trp1, Dct, and Mitf mRNA expressions. Argan oil treatment causes MITF phosphorylation which subsequently inhibited the transcription of melanogenic enzymes, TYR and DCT. The inhibitory effect of argan oil on melanin biosynthesis may be attributed to tocopherols as well as the synergistic effect of its components. The results of this study provide the scientific basis for the traditionally established benefits of argan oil and present its therapeutic potential against hyperpigmentation disorders.

Toxicity Profile of the Aqueous Ethanol Root Extract of Corrigiola telephiifolia Pourr. (Caryophyllaceae) in Rodents.

Corrigiola telephiifolia Pourr. (Caryophyllaceae) is a Moroccan medicinal plant. Despite its popular usage, no study has been published concerning its toxicological profile. The acute toxicity of C. telephiifolia root extract was evaluated by giving it orally to mice at single doses of 5000, 10000, and 14000 mg/kg bodyweight. The extract was also administered at doses of 5, 70, and 2000 mg/kg bodyweight per day to rats for a forty-day toxicity study. No mortality or signs of toxicity were observed in the acute study. In the forty-day study in rats, the extract at 5 mg/kg/day showed no toxicological effects in either sex. At 70 mg/kg/day, the treated group differed from the control only by a significant decrease in serum concentrations of sodium and chloride ions (P < .05). At the dose of 2000 mg/kg/day, the extract significantly increased the serum concentrations of creatinine, alkaline phosphatase, gamma-glutamyltransferase and phosphorus (P < .05) all suggestive of functional nephrotoxicity and hepatotoxicity. The relative bodyweight of both sexes decreased at the dose of 2000 mg/kg/day, with a fast recovery for males. Histological examination did not reveal any treatment-related effects. In conclusion, Corrigiola extract appears safe at the doses used ethno-medicinally. Much higher doses pose toxicological risks.