PD‑L1 expression in malignant melanomas of the skin and gastrointestinal tract

Abstract

Gastrointestinal melanoma (GM) is a rare but aggressive type of malignant melanoma arising in the gastrointestinal tract. An anti-programmed cell death protein 1 (PD-1) antibody markedly improves prognosis in patients with melanoma. However, little is known regarding the expression of immune-oncology biomarkers in GM compared with skin melanoma (SM), especially in the Asian population. the present study examined clinicopathological characteristics, PD-L1 and HLA expression, and immune-oncology marker expression in 10 cases of GM and 31 cases of SM. Patients with GM exhibited significantly higher incidences of lymph node and distant metastases than patients with SM (P=0.0448 and P=0.0247, respectively). The infiltration of CD8 + lymphocytes was significantly higher in GM than in SM (P=0.0231). The infiltration of PD-1 + lymphocytes was higher in GM than in SM, but the difference was not significant (P=0.0975). PD-L1-positive melanoma exhibited a higher proportion of BRAF V600E-positive melanoma than PD-L1-negative melanoma (P=0.0317; 39.4 and 0%, respectively). PD-L1-positive melanoma exhibited significantly higher rates of CD8 + and FOXp3 + lymphocyte infiltration than PD-L1-negative melanoma (P=0.0221 and P=0.0463, respectively). By contrast, PD-1 + lymphocytes did not differ between PD-L1-positive and-negative cases. Furthermore, HLA-positive melanoma exhibited higher proportions of PD-1 (P=0.0101; 53.7 and 15.4%) and CD8 than HLA-negative melanoma (P= 0.0818; 66.7 and 38.2%). These results provided useful information regarding tumor immunity in GM and SM and may contribute to the development of treatment strategies for GM.

Epstein-Barr Virus Lmp1 Enhances Levels of Microvesicle-Associated Pd-L1

“…However, constitutive expression of PD-L1 is far less common than IFN induced PD-L1 expression. PD-L1 is expressed in various cancers: gastric cancer (50), melanoma (51), nasopharyngeal carcinoma (52), posttransplant lymphoproliferative disorder (53), non-small cell lung cancer (54), pancreatic cancer (55), lymphomas (56), bladder cancer (57), kidney cancer (58), breast cancer (59), and Hodgkin lymphoma (60) . Other than EBV, multiple human herpes virus infections have also been found to result in increased PD-L1 expression such as herpes simplex virus (61), Varicella zoster virus (62), Cytomegalovirus (63), Human herpesvirus 6 (64), and Kaposi's sarcoma-associated herpesvirus (65).…”

Distinguishing Brans–Dicke–Kerr type naked singularities and black holes with their thin disk electromagnetic radiation properties

“…For example, the mass can be accurately determined by analyzing the orbits of stars inside the sphere of the gravitational influence of the black hole [131]. An alternative method is represented by the measurement of the diameter of the photon ring encircling the black hole shadow, a method applied for the determination of the mass of M87 * of the radio galaxy M87 [132,133].…”

“…EHT is a global very long baseline interferometry (VLBI) array observing at 1.3 mm. EHT observations of M87 * have recently provided the first-ever horizon-scale image of a black hole [132,133,[135][136][137][138]. These observations show the possibility of the EHT for probing the black hole geometry by timely and spatially resolving the electromagnetic emission coming near the event horizon of black holes.…”

“…Nevertheless, we expect that with the significant improvement of the already existing imaging observational techniques [132,133,[135][136][137][138], it will also be possible to obtain definite observational information about the existence of non-trivial black holes or of naked singularities, and to differentiate these important classes of compact general relativistic objects.…”

Note on the mass–radius relations for spherical compact objects in general relativity with semi-classical corrections

“…While until some years ago the answer to both questions was in the negative, in recent times the possibility to test the regime where the relativistic description may fail has come within our experimental reach. This is thanks to the observation of gravitational waves from binary mergers [66][67][68][69] by the LIGO collaboration and the 'image' of a supermassive black hole candidate by the Event Horizon Telescope collaboration [70]. In particular, the observation of neutron stars mergers is already providing data on the nature and properties of compact objects [71][72][73].…”