Melanoma is a deadly tumor which in recent years has been successfully treated with immune checkpoint inhibitors as PD-1/PD-L1 and CTLA-4 inhibitors and targeted therapy as BRAF and MEK inhibitors.
More importantly, the CA<sub>cluster</sub><i>in vivo</i> improved the tumor response to the PD1/PD-L1 immune checkpoint blockade in melanoma and colon cancer.
PD-L1 positivity was observed in 33% and 39% of primary melanomas and matched metastases, respectively, with, however, poor concordance between the primary and the matched metastatic site (κ = 0.283).
PD-1/PD-L1 blockade in NSCLC and UC increase the risk of immune-related liver dysfunction, but not in melanoma (MM) and head-neck squamous cell carcinoma (HNSCC).
Since 2014, programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) checkpoint inhibitors have been approved by various regulatory agencies for the treatment of multiple cancers including melanoma, lung cancer, urothelial carcinoma, renal cell carcinoma, head and neck cancer, classical Hodgkin lymphoma, colorectal cancer, gastroesophageal cancer, hepatocellular cancer, and other solid tumors.
Anti-PD-1 or anti-PD-L1 therapy has induced tumor regression and improved clinical outcome in patients with different tumor entities, including melanoma, non-small-cell lung cancer, and renal cell carcinoma.
Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells' expression of PD-L1 was seen in 17 carcinomas and 6 melanomas.
Here, we present two "real-world" melanoma cases that were treated in our department with blockade of PD-1/PD-L1 and developed active Mycobacterium tuberculosis (MTB) during immunotherapy.
This review focuses on the recent development of biomarkers for assessing the efficacy of anti-PD1 antibodies using routine blood tests such as the neutrophil-to-lymphocyte ratio, eosinophil ratio, serum markers such as lactate dehydrogenase, programmed cell death ligand 1 (PD-L1) expression on melanoma cells, microsatellite instability and mismatch repair deficiency assays, as well as soluble CD163, and tumor-associated macrophage-related chemokines (e.g., CXCL5, CXCL10).
The median CD8 tumor-infiltrating lymphocyte density was significantly higher in vulvar/vaginal than cervical melanomas and correlated with PD-L1 expression.
In addition, CDK4/6 inhibitor (palbociclib) treatment increased PD-L1 protein levels and enhanced efficacy (<i>P</i> < 0.05) in the C57BL/6-hPD-1 melanoma cell and the HIS PDX model.
Immune checkpoint inhibitors (ICIs), including inhibitors of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) have demonstrated prominent clinical benefits in a variety of cancers and have been rapidly applied to treat a variety of carcinomas such as melanoma, non-small-cell lung cancer, and head and neck cancer.
PD-L1 and the number of tumor infiltrating lymphocytes (TILs) were investigated in 63 Korean patients with melanoma based on the melanoma scoring system.
SPECT/CT imaging in mice following intravenous injection of Technetium-99m (<sup>99m</sup>Tc)-labeled sdAb K2 revealed high signal-to-noise ratios, strong ability to specifically detect PD-L1 in melanoma and breast tumors, and relatively low kidney retention, which is a unique property for radiolabeled sdAbs.
In this international, randomised, placebo-controlled, double-blind, parallel-group, phase 3 trial, eligible participants were aged 18 years or older, with unresectable stage III or IV melanoma previously untreated with PD-1 or PD-L1 checkpoint inhibitors, an ECOG performance status of 0 or 1, and had a known BRAF<sup>V600</sup> mutant status or consented to BRAF<sup>V600</sup> mutation testing during screening.
Pembrolizumab has already proven its efficacy and thus obtained marketing authorization in so-called hot or hypermutated tumors or tumors expressing PD-L1 such as melanomas, non-small cell lung cancers, urothelial carcinomas, cervical cancer, etc.
Melanoma treatment has progressed in the past decade with the development and approval of immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand (PD-L1) and cytotoxic T lymphocyte-associated antigen 4, as well as small molecule inhibitors of BRAF and/or MEK for the subgroup of patients with BRAF<sup>V600</sup> mutations<sup>1-9</sup>.
In recent years, treatment of melanoma and a range of other deadly cancers has involved immunotherapy with programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) checkpoint blockade which has improved survival.