Immunotherapy for renal cell carcinoma

Abstract

Immunotherapy plays a significant role in the management of renal cell carcinoma (RCC) patients with metastatic disease because RCC is highly resistant to both chemotherapy and radiation therapy. Many reports illustrate various approaches to the treatment of RCC, such as cytokine-, antigen- or dendritic cell- (DC-) based immunotherapy, and the safety and effectiveness of immunotherapy have been highlighted by multiple clinical trials. Although antitumor immune responses and clinically significant outcomes have been achieved in these trials, the response rate is still low, and very few patients show long-term clinical improvement. Recently, the importance of immune regulation by antigen-presenting cells (APC) and regulatory T cells (Treg cells) has also been discussed. The authors outline the principles of cell-mediated tumor immunotherapy and discuss clinical trials of immunotherapy for RCC.

Figure 1

CTL induction by Apcs. Antigens are taken up and degraded into peptide fragments by antigen presenting cells (APC), such as immature DC. At some point on their path to the cell surface, newly synthesized MHC class II or I molecules bind the peptide antigen fragments and transport the peptides to the cell surface. CD8⁺ T cells recognizing the antigen expressed by weakly costimulatory cells become activated only in the presence of CD4⁺ T cells bound to the same APC. This happens via CD4⁺ T cells recognizing antigens presented by APCs and being triggered to induce increased levels of costimulatory activity by the antigen-presenting cell. The CD4⁺ T cells also produce increased amounts of IL-2, which drives CD8⁺ T cell proliferation. CD8⁺ T cells then become cytotoxic T lymphocytes (CTL).