From foes to friends: rethinking the role of lymph nodes in prostate cancer

Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly 'foes' or whether they are actually 'friends' in oncological care is an important idea to discuss. Pelvic lymph node dissection is performed for staging and to prevent recurrence of prostate cancer; however, immune checkpoint inhibition could be affected by lymph node removal. Here, the authors discuss the possibility that lymph nodes could be 'friends' rather than 'foes' in prostate cancer treatment.