Tumor-draining lymph nodes: opportunities, challenges, and future directions in colorectal cancer immunotherapy

Abstract

Tumor-draining lymph nodes (TDLNs) are potential immunotherapy targets that could expand the population of patients with colorectal cancer (CRC) who may benefit from immunotherapy. Currently, pathological detection of tumor cell infiltration limits the acquisition of immune information related to the resected lymph nodes. Understanding the immune function and metastatic risk of specific stages of lymph nodes can facilitate better discussions on the removal or preservation of lymph nodes, as well as the timing of immunotherapy. This review summarized the contribution of TDLNs to CRC responses to immune checkpoint blockade therapy, local immunotherapy, adoptive cell therapy, and cancer vaccines, and discussed the significance of these findings for the development of diagnostics based on TDLNs and the potential implications for guiding immunotherapy after a definitive diagnosis. Molecular pathology and immune spectrum diagnosis of TDLNs will promote significant advances in the selection of immunotherapy options and predicting treatment efficacy.

High expression of PD-L1 on conventional dendritic cells in tumour-draining lymph nodes is associated with poor prognosis in oral cancer

“…Compared to HLN, n-TDLN, and TDLN exhibited increased memory cell differentiation and signs of exhaustion, indicating that T-cell activation and expansion of T-cell mediated anti-tumor immunity is not restricted to TDLN alone. While TDLNs are considered the primary source of tumor-reactive T-cells and targets for immune therapeutic interventions [ 45 ]. n-TDLN also represents an opportunity for local cancer treatment.…”

Jagged-1+Tregs Mediate Lymphatic Remodeling in Tumour-Draining Lymph Nodes

“…Syngeneic tumour model 2 × 10 5 B16F10 tumour cells mixed with matrigel at 1:1 ratio were intradermally injected into the left flank of 6-11 week old Foxp3-DTR (Jackson Laboratory) and Foxp3 eGFP-Cre-ERT2 Jag1fl/fl or fl/wt female mice. Tumour size was measured by digital caliper every 3 days and animals were sacrificed and lymph nodes and tumours were collected at various time points.…”

“…3,4 This enrichment poses clinical opportunities for local tdLN immunotherapies, an alternative to targeting tumours with a higher immunosuppressive status. 5 Tumour development is accompanied by tdLN enlargement and lymphatic remodelling to favour a pre-metastatic lymphovascular niche conducive to tumour cell colonization. 6 Lymphatic vessels are vital for maintaining the structural and functional stability of the lymph node in an organotypic manner.…”

“…3,4 This enrichment poses clinical opportunities for local tdLN immunotherapies, an alternative to targeting tumours with a higher immunosuppressive status. 5…”