Cancer immunotherapy responses persist after lymph node resection

Abstract

AbstractDue to the critical role of lymph nodes (LNs) in the initiation and maintenance of adaptive immune responses, it is unclear whether surgical removal or ablative radiation therapy of LNs should be performed in patients with metastatic LNs that will receive immunotherapy. Surgical removal of LNs to prevent metastatic recurrence, including sentinel lymph node biopsy (SLNB) and completion lymph node dissection (CLND), are performed in routine practice. However, removing LNs eliminates opportunities for generating anti-cancer immune responses that are enhanced with immune checkpoint blockade (ICB). Balancing the potential risks and benefits of LN surgery is necessary to maximize outcomes for patients. In contrast to mouse studies using ectopic tumor implantation1,2, the phase III clinical trialNCT00636168found patients with completely resected stage III melanoma (primary tumor, sentinel LNs and disease-related LNs all removed) still benefited from anti-CTLA4 inhibition. Our retrospective analysis demonstrated that stage III melanoma patients with SLNB or CLND have similar response to anti-PD1 inhibition. Using orthotopic murine mammary carcinoma and melanoma that have spontaneous LN metastases, we show that responses to ICB persist in mice after resection of TDLNs.