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Updated: Jan 10, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Targeting Neuropilin-1 to Enhance Immunotherapy in Melanoma: Reducing Peripheral Treg-Mediated Immunosuppression and
Somlata Khamaru1,2, Kshyama Subhadarsini Tung1,2, Subhasis Chattopadhyay1,2
1School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, Odisha, India.
Abstract:
Melanoma, a highly aggressive skin cancer, ranks fifth among Caucasians and has a high mutation rate. Despite advances in immunotherapy, over 40% of patients face immune-related side effects. Neuropilin-1 (NRP1), which is overexpressed in various cancers, enhances the function of Treg cells and promotes tumour growth, thereby contributing to poor patient outcomes. This study investigated the effects of NRP1 inhibition in B16-F10 melanoma, with a focus on its impact on immune responses regulated by peripheral T regulatory cells (Tregs). NRP1 was found to be overexpressed in the majority of cancer patient samples and cancer cell lines, including melanoma, as indicated by cBioPortal and the human protein atlas database analysis, establishing a positive correlation between NRP1 and various cancers. mRNA studies revealed elevated NRP1 expression in tumorigenic B16-F10 cells compared with non-tumorigenic NIH-3T3 cells. Inhibition of NRP1 induced apoptosis in B16-F10 cells without affecting NIH-3T3 cells. It also reversed the immunosuppression caused by B16-F10-cell culture supernatant (B16-F10-CS), reducing the Treg population (NRP1, NKG2A, and FOXP3), Treg suppressive activity and the secretion of immunomodulatory cytokines (IL-10 and IL-17A) while increasing T cell proliferation and the secretion of effector cytokines (TNF, IFN-γ, IL-6, and IL-2). Additionally, NRP1 inhibition suppressed the STAT, ERK MAPK, and Smad2/3 pathways and activated the PI3K/AKT pathway in Tregs cultured in B16-F10-CS in vitro. In tumour-bearing mice, NRP1 inhibition decreased Treg and Th2 population marker expression and enhanced T cell proliferation and Th1 population marker expression in peripheral Tregs. It also reduced lung metastasis, decreased tumour size, and improved survival. These findings suggest that targeting NRP1 could slow melanoma progression and reduce peripheral Treg-mediated immunosuppression, making it a promising approach for future cancer immunotherapies, especially in combination with other treatments.
Insights
Inhibiting Neuropilin-1 (NRP1) in melanoma reduces immunosuppression by T regulatory cells (Tregs). This targeted approach slows tumor growth, decreases metastasis, and improves survival, offering a promising cancer immunotherapy strategy.
Area of Science:
- Immunology and Cancer Research
- Molecular Biology and Oncology
Background:
- Melanoma is an aggressive skin cancer with a high mutation rate and significant unmet treatment needs, particularly concerning immune-related side effects of immunotherapy.
- Neuropilin-1 (NRP1) is overexpressed in many cancers, including melanoma, where it promotes tumor growth by enhancing regulatory T cell (Treg) function, leading to poor patient outcomes.
Purpose of the Study:
- To investigate the therapeutic potential of Neuropilin-1 (NRP1) inhibition in B16-F10 melanoma.
- To evaluate the impact of NRP1 inhibition on immune responses mediated by peripheral T regulatory cells (Tregs).
Main Methods:
- Analysis of NRP1 expression in cancer databases and cell lines.
- In vitro studies involving B16-F10 melanoma cells and NIH-3T3 cells to assess apoptosis and immune modulation.
- In vivo studies using tumor-bearing mice to evaluate the effects of NRP1 inhibition on tumor progression, metastasis, and survival.
Main Results:
- NRP1 inhibition induced apoptosis in melanoma cells and reversed immunosuppression by B16-F10 cell supernatant, reducing Treg populations and suppressive activity.
- NRP1 inhibition modulated cytokine secretion, enhanced T cell proliferation, suppressed key signaling pathways (STAT, ERK MAPK, Smad2/3), and activated the PI3K/AKT pathway in Tregs.
- In vivo, NRP1 inhibition decreased Treg and Th2 markers, increased T cell proliferation and Th1 markers in peripheral Tregs, reduced lung metastasis, tumor size, and improved survival.
Conclusions:
- Targeting Neuropilin-1 (NRP1) effectively slows melanoma progression and counteracts peripheral Treg-mediated immunosuppression.
- NRP1 inhibition presents a promising strategy for melanoma immunotherapy, potentially enhancing efficacy when combined with other treatments.
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