Mechanisms of resistance to immune checkpoint inhibitors in melanoma: What we have to overcome?

Self-supplying Cu2+ and H2O2 synergistically enhancing disulfiram-mediated melanoma chemotherapy

“…Melanoma, one of the skin cancers with a high mortality rate, is seriously threatening to human health. [1][2][3][4][5][6][7][8] Surgery shows very limited efficacy for advanced melanoma, and classic treatments such as chemotherapy and targeted therapy are very costly and have side effects. [9][10][11] Herein, a new treatment is proposed for advanced melanoma using clinically approved "old drugs", 12,13 with reduced clinical trial time and high biosafety.…”

CD4 T cells and toxicity from immune checkpoint blockade

“…Over the last decade, immune checkpoint inhibitors (ICIs) have revolutionized clinical oncology, yielding impressive gains in progression‐free and overall survival in patients with metastatic melanoma, 1–4 lung cancer, 5–8 and other malignancies 9–11 . Currently, there are 11 FDA‐approved monoclonal antibody‐based ICI therapies that boost antitumor immunity via blockade of inhibitory signaling in the tumor microenvironment 12,13 . Such agents include antibodies that target cytotoxic T lymphocyte antigen 4 (CTLA‐4), programmed cell death 1 (PD‐1) or its ligand (PD‐L1), and more recently, lymphocyte activation gene 3 (LAG‐3) 14 .…”

“…[9][10][11] Currently, there are 11 FDA-approved monoclonal antibody-based ICI therapies that boost antitumor immunity via blockade of inhibitory signaling in the tumor microenvironment. 12,13 Such agents include antibodies that target cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1) or its ligand (PD-L1), and more recently, lymphocyte activation gene 3 (LAG-3). 14 Building upon this success, many studies are now underway to identify and translate novel immunomodulatory signaling axes and ICI treatment combinations.…”

BCKDHA contributes to melanoma progression by promoting the expressions of lipogenic enzymes FASN and ACLY

“…7,8 Nevertheless, the 5-year survival of those with metastasis remains far from satisfaction, mainly resulting from low response rate and the inevitable occurrence of treatment resistance to current available therapeutic methods. 9,10 Therefore, it is necessary to cultivate alternative treatment options based on the forward elucidation of the underlying mechanism of melanoma progression.…”

“…In the past few decades, due to the revolutionary advances in the development of targeted therapy and immunotherapy, 5,6 the prognosis of patients with melanomas have gained unprecedented progress 7,8 . Nevertheless, the 5‐year survival of those with metastasis remains far from satisfaction, mainly resulting from low response rate and the inevitable occurrence of treatment resistance to current available therapeutic methods 9,10 . Therefore, it is necessary to cultivate alternative treatment options based on the forward elucidation of the underlying mechanism of melanoma progression.…”