Abstract
Lymph nodes are secondary lymphoid organs that appear as bean-like nodules usually <1 cm in size, and they are localized throughout the body. Many antigen-presenting cells such as dendritic cells and macrophages reside in lymph nodes, where they mediate host defense responses against pathogens such as viruses and bacteria. In cancers, antigen-presenting cells induce cytotoxic T lymphocytes (CTLs) to react to cancer cell-derived antigens. Macrophages located in the lymph node sinus are of particular interest in relation to anti-cancer immune responses because many studies using both human specimens and animal models have suggested that lymph node macrophages expressing CD169 play a key role in activating anti-cancer CTLs. The regulation of lymph node macrophages therefore represents a potentially promising novel approach in anti-cancer therapy.
Highlights
Anti-programmed death 1 (PD-1) and anti-CTLA-4 therapy are reportedly effective for patients with several types of solid tumors, such as melanoma, non-small-cell lung cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma (SCC), esophageal SCC, gastric adenocarcinoma, triple-negative breast carcinoma, and microsatellite instability-high tumors [4]
Dammeijer et al detected expression of programmed death ligand 1 (PD-L1) in dendritic cells (DCs) and macrophages in tumor-draining lymph nodes; blocking PD-L1 on DCs induced an effective anti-tumor immune response [9]. These authors found greater interaction between PD-1 and PD-L1 in the lymph nodes than tumors, which correlated with shorter relapse-free survival. These findings suggest that tumordraining lymph nodes play a critical role in the anti-tumor immune responses induced by anti-PD1/PD-L1 therapy in the early stage of diseases
Summary
Cancer cells are characterized by the accumulation of a variable number of genetic alterations that result in the production of neoantigens. Dammeijer et al detected expression of PD-L1 in DCs and macrophages in tumor-draining lymph nodes; blocking PD-L1 on DCs (but not macrophages) induced an effective anti-tumor immune response [9]. These authors found greater interaction between PD-1 and PD-L1 in the lymph nodes than tumors, which correlated with shorter relapse-free survival. These findings suggest that tumordraining lymph nodes play a critical role in the anti-tumor immune responses induced by anti-PD1/PD-L1 therapy in the early stage of diseases
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