The procedure scheme is shown in Fig.?4a. was prolonged from 11 to 16?times as well as the median success period was even prolonged 7.5?days relative to the control group (NS group). Nanovaccines improved neoantigen-specific T cells RPH-2823 to 10-fold of free vaccines, and upregulated Th1 cytokines, such as IFN- and TNF-. The anti-tumor activity of spleen lymphocytes in the nanovaccine group was significantly stronger than that of additional groups. However, some immune-inhibitory cells or molecules in tumor microenvironment have been recognized upregulated under the immune pressure of neoantigen nanovaccines, such as Tregs and PD-L1. The effectiveness of the neoantigen nanovaccine combined with anti-PD1 antibody or Treg inhibiting peptide P60 was better than that of the solitary treatment. Conclusions We developed a general vaccine strategy, triggering specific T cell reactions, and offered feasible combination strategies for better anti-tumor effectiveness. Graphical abstract Supplementary Info The online version contains supplementary material available at 10.1186/s12951-022-01397-7. strong class=”kwd-title” Keywords: Neoantigen, Malignancy vaccine, Nanoparticle, Immunotherapy, Anti-PD1 LRP10 antibody antibody Intro Melanoma is the most lethal pores and skin cancer and the effectiveness of immune checkpoint inhibitors (ICIs) on it is not adequate. Individuals with metastatic melanoma experienced an objective response rate (ORR) of only 10.9% with ipilimumab [1] and a 5-year survival rate of 41% with pembrolizumab [2]. To improve the effectiveness of immunotherapy or overcoming drug resistance, the strategies include changing chilly tumors (low mutation weight and less tumor infiltrating lymphocytes) into sizzling tumors, removing immunosuppressive factors and so on. At present, the malignancy vaccine is an active area, can induce and amplify tumor-specific T cell reactions and form long-term immune memory, providing bright prospect of medical application [3]. However, only one restorative vaccine Provenge has been authorized by USA food and drug administration (FDA) for the treatment of prostate cancer, and many cancer vaccine medical trials have moderate effectiveness [4]. As we previously reviewed, selection of antigens is the key factor of the medical effectiveness of malignancy vaccines [5]. Neoantigens, produced by mutant proteins or oncogenic viruses integrated into the genome, without thymus bad screening and only indicated in tumor cells, are currently recognized as the ideal focuses on for malignancy vaccines [6]. With the development of next-generation sequencing and bioinformatics, it is possible to determine neoantigens for individuals. Personalized RPH-2823 neoantigen vaccines have begun to accomplish good effectiveness in small-scale early medical trials [7C9]. Most antigens utilized by vaccines are proteins, peptides or nucleic acids, which have poor stability in vivo. In order to play an anti-tumor part, vaccines need to be efficiently delivered to secondary lymphoid organs, in which immune reactions primarily happen. The nanomaterial transporting both tumor antigens and adjuvants, is one of the most common and successful methods to activate antitumor immune reactions, due to the ability to target tumors, lymph nodes, or antigen showing cells (APCs). In addition, the protective effect of nanomaterials on loaded medicines makes the types of antigens available for tumor vaccines more abundant [10]. In general, the immune system uses major histocompatibility complex (MHC) class II pathway to remove extracellular soluble non-selfantigens [11]. Different from extracellular soluble antigens, the antigens on extracellular nanoparticles often undergo a cross-presentation process after becoming ingested by APCs, and are loaded on RPH-2823 MHC I and offered to CD8+ T cells, the main force to destroy tumor cells [12, 13]. Restorative tumor vaccines still face unique tumor microenvironment difficulties. Solid tumors often obtain immune escape, grow and metastasize rapidly by inducing hypoxia and low pH in the microenvironment, expressing immunosuppressive molecules, such as programmed cell death protein 1 ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and recruiting immunosuppressive cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). ICIs are monoclonal antibodies against checkpoint proteins indicated by immune cells or tumor cells, which can reactivate T cell reactions by obstructing immunosuppressive transmission pathways [14C16]. More and more evidence supports the look at that if tumor individuals lack pre-existing tumor infiltrating lymphocytes (TILs), they may be unlikely to benefit from ICIs treatment [17, 18]. Based on the RPH-2823 abilities of malignancy vaccines to induce and amplify TILs, restorative vaccines and ICIs may have.