A Milestone in the Shift from "Passive Killing" to "Active Immunomodulation" in Cancer Treatment-Progress in Melanoma Vaccine Research.

Opinion statement: Melanoma is the most malignant skin tumor and exhibits extremely aggressive behavior with a high tendency to metastasize. Although the 5-year survival rate of early-stage patients (stage I-II) can reach over 90%, intermediate- and late-stage patients (stage III-IV) still face a high risk of recurrence and metastasis even after surgical resection. Moreover, these patients show low sensitivity to traditional therapies such as chemotherapy and radiotherapy. While immune checkpoint therapies (ICIs) represented by PD-1 inhibitors have significantly improved patient prognosis, they remain ineffective in 30%-40% of cases due to tumor immune escape or microenvironmental suppression. Additionally, long-term use of ICIs may induce autoimmune side effects (e.g., thyroid dysfunction). Therefore, there is an urgent need to develop more precise and durable treatment strategies. Vaccines for the treatment of melanoma represent one of the most promising therapeutic approaches. Melanoma vaccines activate the immune system through antigen recognition, leading to precise tumor killing. The vaccine also induces immune memory, demonstrates safety, and can be combined with immune checkpoint inhibitors to significantly enhance efficacy-making it a vital treatment for postoperative high-risk patients in their pursuit of long-term disease-free survival. With theoretical breakthroughs and technological iterations in immunotherapy, the development of melanoma vaccines has thrived and shown encouraging efficacy in clinical trials. Current mainstream melanoma vaccines are categorized into cell-based, peptide, nucleic acid, and viral types. Remaining challenges include complex and costly production processes, individual variability in therapeutic response, limited efficacy in advanced-stage patients, and potential autoimmune risks. Although melanoma vaccines face many shortcomings and challenges, these difficulties are being actively addressed through innovative strategies. For example, mRNA vaccine optimization involves improving stability and immunogenicity while shortening preparation cycles via enhanced lipid nanoparticle delivery and antigen design; novel vaccine platforms include nanovaccines and phage vaccines; combination therapy strategies entail combining vaccines with immune checkpoint inhibitors or targeted therapies; and using multi-omics analysis and AI to predict neoantigens, screen patients most likely to benefit, and develop efficacy monitoring markers to optimize treatment regimens. Although most melanoma vaccines are still under research, their emergence exemplifies the realization of individualized precision medicine and marks a milestone in the shift from "passive killing" to "active immunomodulation" in cancer treatment. This study provides an overview of recent research on melanoma vaccines to enable readers to grasp the latest advances in this field.