Identification of Programmed Death Ligand 1–derived Peptides Capable of Inducing Cancer-reactive Cytotoxic T Lymphocytes From HLA-A24+ Patients With Renal Cell Carcinoma

Abstract

Molecular therapy targeting tumor angiogenesis has been the standard treatment for metastatic renal cell carcinoma (mRCC). However, despite their significant antitumor effects, most of patients with mRCC have not been cured. Under such circumstances, anticancer immunotherapy has been considered a promising treatment modality for mRCC, and cancer-reactive cytotoxic T lymphocytes (CTLs) are the most powerful effectors among several immune cells. However, anticancer CTLs can be inhibited by several immune inhibitory mechanisms, including the interaction between programmed death 1 (PD-1) and its ligand PD-L1, on T cells and cancer cells, respectively. Alternatively, this also means that PD-L1 could be a promising target for anticancer immunotherapy. Therefore, we searched for PD-L1-derived peptides that are applicable for anticancer vaccine for HLA-A24(+) RCC patients. Among 5 peptides derived from PD-L1, which were prepared based on the binding motif to the HLA-A24(+) allele, both PD-L1(11-19) and PD-L1(41-50) peptides induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24(+) RCC patients. Such PD-L1 peptide-stimulated CD8 T cells showed cytotoxicity against HLA-A24(+) and PD-L1-expressing RCC cells. Although IFN-γ treatment increased PD-L1 expression on PD-L1(low) RCC cells, their sensitivity to cytotoxicity of PD-L1 peptide-stimulated CD8(+) T cells varied between patients. Altogether, these results indicate that both PD-L1(11-19) and PD-L1(41-50) peptides could be candidates for peptide-based anticancer vaccines for HLA-A24(+) mRCC patients.

Systemic immune-inflammation index predicts the clinical outcome in patients with metastatic renal cell cancer treated with sunitinib

“…Neutrophils can promote adhesion and tumoral seeding through the secretion of circulating growth factors [17, 18]. Lymphocytes display a significant antitumoral role by inducing cytotoxic cell death and inhibiting tumor cell proliferation and migration, instituting the host's immune response to cancer [19–20]. Therefore, inflammation deeply influences cancer microenvironment that supports cancer progression.…”

Detection of an Immunogenic HERV-E Envelope with Selective Expression in Clear Cell Kidney Cancer

“…Recently, PD-L1 molecule which is expressed at high level in various cancer types including RCC was chosen as a target for anticancer immunotherapy. Minami et al identified new HLA-A24+ restricted PD-L1 peptides that could be used for peptide-based anticancer vaccines for metastatic RCC patients (24). One of the limitations to implementing this approach is expression of PD-L1 on non-cancer cells, with the risk that PD-L1-recognizing CTLs could attack normal cells.…”

The clinical use of the platelet/lymphocyte ratio and lymphocyte/monocyte ratio as prognostic predictors in colorectal cancer: a meta-analysis

“…Lymphocytes represent the cellular basis of cancer immunosurveillance. Compelling evidence indicates that lymphocytes induce cytotoxic cell death and inhibit tumor cell proliferation and migration, thereby dictating the host's immune response to cancer [55]. Decreased lymphocyte counts may lead to downregulation of the immune response against cancer.…”