Like IL-2, IFN- therapy can also cause toxic reactions, such as fatigue, weakness, fever, chills and myalgia, depression, elevated transaminase, and autoimmunity (144)

Like IL-2, IFN- therapy can also cause toxic reactions, such as fatigue, weakness, fever, chills and myalgia, depression, elevated transaminase, and autoimmunity (144). by interfering with its CD27 receptor and intracellular SIVA protein binding, rendering it difficult for patients to develop an efficient lymphocyte-mediated anti-tumor response (112). The above findings indicate that this mechanism of tumor-induced T cell apoptosis is usually receptor-dependent, so researchers turn their attention to soluble tumor-derived factors and predict whether T cell apoptosis can be independently induced by the receptor. Kudo et al. (113) found that gangliosides in the RCC cell line supernatant (SK-RC-45) were involved in tumor-induced T cell apoptosis through reduction of Bcl-2 and Bcl-XL expressions in lymphocytes, the release of cytochrome c and the activation of caspase in mitochondria simultaneously. In summary, renal cell carcinoma tumors can induce T cell apoptosis by synthesizing products of both receptor-dependent and receptor-independent pathways, and by activating both impartial apoptotic pathways. There are a variety of explanations for immune escape and tumor development in renal cell carcinoma. Table 1 summarizes the basic mechanisms of immune escape, including the expression of HLA-I molecules and changes in cytokines. A variety of immunosuppressive cytokines and immunosuppressive cells in TME of renal cell carcinoma generate inhibitory conditions to inhibit congenital or adaptive immune responses, creating conditions conducive to tumor escape (Physique 1). Table 1 Immune escape mechanisms in renal cell carcinoma. = 204) or sunitinib monotherapy (= 135). Vaccination with IMA901 plus granulocyte macrophage colony-stimulating factor in addition to first-line sunitinib did not prolong OS relative to sunitinib alone in patients with advanced, previously untreated metastatic renal cell carcinoma. Unlike the results of the Phase IPI-549 II study, the magnitude of the CD8+ T cell response is very low in the phase III study, which could be triggered by an adverse inhibition of the T cell activation induced by sunitinib or IMA901 or both. In summary, the IMA901 peptide vaccine administered with GM-CSF and single-dose cyclophosphamide exhibited increased clinical benefit in patients with RCC. The rational use of adjuvants makes Nrp2 peptide vaccines more effective, and the combination of tumor vaccines and targeted therapies offers a promising approach to the treatment of renal cell carcinoma. Future research should concentrate on how to enhance the conditions for improving the OS. Efficacy of autologous tumor-derived heat shock protein (glycoprotein 96)-peptide complex (HSPPC-96; vitespen) vaccine was assessed in a randomized phase III trial in patients at high risk of recurrence following resection of locally advanced renal cell carcinoma and there was no difference in recurrence-free survival (RFS) between patients treated with vitespen after nephrectomy and those not treated (120). The basic antigen G250 (carbonic anhydrase IX; IPI-549 CAIX) is usually expressed on the surface of 75% of RCC cells (90% of clear renal cell carcinoma) but has minimal expression in normal cells (121, 122), so that it can become one of the possible therapeutic targets. Tso et al. (123) identified a novel strategy for RCC vaccines that developed a fusion protein (FP) capable of delivering dual immune activators simultaneously: G250 and GM-CSF. The fusion protein GM-CSF-G250 obtained from the baculovirus expression vector system is usually a potent immunostimulant with the ability to activate immunomodulatory DCs and to induce T-helper cell-supported, G250-targeted and CD8+-mediated anti-tumor response. This completely suggests the efficacy of GM-CSF-G250 FP as an RCC cancer vaccine and can be used in clinical trials to treat advanced RCCs in the future. Dendritic Cell Vaccines DCs are known to IPI-549 be a powerful antigen presenting cell in human body, and they are the initiator of anti-infection and anti-tumor immunity. Based on IPI-549 the strong immune properties of DCs, the DC vaccine has been established. The method of administering the DC vaccine to patients with renal cell carcinoma.