Combination immunotherapy with interleukin‐2 surface‐modified tumor cell vaccine and programmed death receptor‐1 blockade against renal cell carcinoma

Abstract

Immunotherapy may be an effective way to prevent postoperative recurrence of renal cell carcinoma. Streptavidin‐interleukin‐2 (SA‐IL‐2) surface‐modified tumor cell vaccine developed through our protein‐anchor technology could induce specific antitumor T‐cell responses, but this immunotherapy cannot completely eradicate the tumor. These effector T cells highly expressed programmed death receptor‐1 (PD‐1), and the expression of programmed death ligand‐1 (PD‐L1) in the tumor environment also was upregulated after SA‐IL‐2‐modified vaccine therapy. PD‐1/PD‐L1 interaction promotes tumor immune evasion. Adding PD‐1 blockade to SA‐IL‐2‐modified vaccine therapy increased the number of CD4+, CD8+ and CD8+interferon‐γ+ but not CD4+Foxp3+ T cells. PD‐1 blockade could rescue the activity of tumor‐specific T lymphocytes induced by the SA‐IL‐2‐modified vaccine. Combination therapy delayed tumor growth and protected mice against a second Renca cells but not melanoma cells challenge. Taken together, PD‐1 blockade could reverse immune evasion in the treatment with SA‐IL‐2‐modified vaccine, and eventually induce a stronger specific antitumor immune response against renal cell carcinoma.

High expression of RNF169 is associated with poor prognosis in pancreatic adenocarcinoma by regulating tumour immune infiltration

“…The efficacy of immunotherapy depends on infiltrated immune cells and the expression of immune checkpoint molecules in the TME ( Zhang et al, 2019 ; Huang et al, 2020 ). Thus, we evaluated the correlation between RNF169 and immune checkpoints and found that high expression of RNF169 was associated with CTLA4 or CD274, indicating that targeting RNF169 may be a potential approach to improve the efficacy of immunotherapy for PAAD.…”

Therapeutic vaccination immunomodulation: forming the basis of all cancer immunotherapy

“…109 IL-2 has been combined with a range of other therapies including imiquimod, with a reported 100% intralesional CR rate 110 and anti-PD-1 therapy. 111 The highest CR rate of 5.0% was associated with IL-2 combined with vaccine therapy in RCC. 104 In a separate study, topical daily application of 5% imiquimod cream (Aldara, Bausch, Quebec, Canada) was undertaken for 4 weeks to superficial melanoma lesions, followed by IL-2 injected either intralesionally, subcutaneously or a combination of both, according to three regimens.…”

PD‐1/PD‐L1 inhibitors‐based treatment for advanced renal cell carcinoma: Mechanisms affecting efficacy and combination therapies

“…PD‐1/PD‐L1 mAbs could reverse this immune escape, promote IFN‐γ and IL‐12 expression, and further enhance the cytotoxicity of specific antitumor T cells. 112 Moreover, glutamine‐addicted ccRCC depletes extracellular glutamine and then upregulates HIF‐1α expression, thereby inducing tumor‐infiltrating macrophages to secrete IL‐23. It could promote IL‐10 and TGF‐β expression and then decrease the IFN‐γ, GZMB, and PRF1 expression levels on CD8+ T cells to inhibit their cytotoxicity; thus, IL‐23 inhibitors also have a synergistic effect with PD‐1 mAbs.…”