Blocking immune checkpoints in prostate, kidney, and urothelial cancer: An overview

Abstract

Despite a long history of immunotherapeutic approaches to treatment, most genitourinary malignancies are not cured by existing immunotherapy regimens. More recently, cell-surface molecules known as immune checkpoints have become the focus of efforts to develop more effective immunotherapies. Interactions between these molecules and their ligands inhibit the proliferation and function of tumor-specific lymphocytes. A monoclonal antibody blocking one of these checkpoints was approved for the treatment of metastatic melanoma and is now being tested in other malignancies. The objective responses seen in these early trials of checkpoint blockade are driving renewed enthusiasm for cancer immunotherapy. There are several ongoing and planned trials in genitourinary malignancies of single-agent inhibitors, as well as combinations targeting multiple checkpoints or adding other types of therapies to checkpoint blockade.

Jagged1 upregulation in prostate epithelial cells promotes formation of reactive stroma in the Pten null mouse model for prostate cancer

“…Men with castration resistant prostate cancer did not respond to immune checkpoint therapy as a monotherapy because of several potential mechanisms such as low expression level of PD-L1 in tumor cells or inefficient infiltration of CD8 + T cells (45). Inflammatory cytokines such as IFNγ has been shown to upregulate PD-L1 (46).…”

Role of routine computed tomography scan in the oncological follow up of patients treated by radical cystectomy for bladder cancer

“…Cisplatin‐based chemotherapy has been the mainstay for recurrences after RC for decades, with a poor prognosis . In recent years, there has been growing interest in new immunotherapeutic agents, such as immune checkpoint blockades and angiogenesis inhibitors for metastatic bladder cancer, with promising preliminary results . Ongoing phase 3 trials investigating several targeted agents, if positive, could add arguments for an early diagnosis of recurrences .…”

“…18,19 Ongoing phase 3 trials investigating several targeted agents, if positive, could add arguments for an early diagnosis of recurrences. 18,19 Therefore, the challenge of detecting recurrences at an asymptomatic stage might impact the use of CT scan in routine follow up in order to improve the prognosis of metastatic patients after RC.…”

PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity

“…PD-1 is commonly highly expressed on tumor-infiltrating lymphocytes (TILs; Ahmadzadeh et al, 2009). Blocking the interaction of PD-1 with its ligands, PD-L1 and PD-L2, leads to impressive antitumor responses and clinical benefit in a subset of patients (Ribas, 2012; Alme et al, 2016). However, the precise cellular and molecular mechanisms underlying this efficacy are not well understood.…”