Immune‐mediated antitumor effect of a transplanted lymph node

Abstract

Lymph node (LN) transplantation is a recognized method for reconstruction of the lymphatic system and is used in the clinical setting to treat lymphedema. However, it is unclear whether transplanted LNs contribute to immune surveillance. In our study, we investigated whether a single transplanted non-vascularized LN, defined as a tumor-draining transplanted lymph node (TDTLN), could exert an immune-mediated antitumor effect. LN and lung metastases and primary tumor enlargement were evaluated in mice that were inoculated with B16-F10-luc2 melanoma cells in a hind limb footpad without (group 1) and with (group 2) popliteal lymph node (PLN) resection and in mice that underwent LN transplantation after PLN resection (group 3). The function of a TDTLN (group 3) and a tumor-draining popliteal lymph node (TDPLN; group 1) was evaluated in the context of cancer. LN and lung metastases were significantly aggravated by PLN resection but were significantly decreased by LN transplantation. Immunohistochemistry showed that the TDTLNs retained T-cells and B-cells and fluorescence-activated cell sorting analysis confirmed expansion of lymphocytes in these nodes; however, the degree of expansion in TDTLNs was different from that in TDPLNs. Expression of cytokines associated with immunostimulation was confirmed in the TDTLNs as well as in the TDPLNs. One of the differences in the immune-mediated antitumor effect of the TDPLNs and TDTLNs was ascribed to a difference in the site of lymphocyte homing to peripheral LNs through high endothelial venules. Non-vascularized LN transplantation had an immune-mediated antitumor effect.

Feasibility of pedicled vascularized inguinal lymph node transfer in a mouse model: A preliminary study

“…Moreover, a PLN could be regarded as the sentinel lymph node, which is the primary site where the immune system encounters tumor antigens in a mouse model inoculated with B16F10 melanoma cells, syngeneic and transplantable to the C57BL/6 mouse strain, into the hindlimb footpad (Maeda, Hayashi, et al, ). We believe that our model will be useful for further investigating the physiologic and immunologic functions of the transferred vascularized lymph nodes as well as the biological significance of these functions in terms of tumor immunity (Maeda, Hayashi, et al, ; Oashi et al, ; Rabson et al, ).…”

“…A mouse model would be advantageous to investigate the immune function mechanism with numerous antibodies. We recently reported, using a mouse model inoculated with B16F10 melanoma cells, the immune‐mediated antitumor effect of nonvascularized lymph node autotransplantation (Maeda et al, ). However, autotransplantation of lymph nodes is rarely performed in clinical situations because of lymphedema after lymphatic injury during cancer treatment.…”

The Value of the Systemic Immune-Inflammation Index in Predicting Survival Outcomes in Patients with Brain Metastases of Non-Small-Cell Lung Cancer Treated with Stereotactic Radiotherapy

“…and lymphocytes) can regulate the balance of the host inflammatory and immune status, which are associated with prognostic value in multiple tumor types[34][35][36][37][38]. Several mechanisms can potentially explain why peripheral blood parameters statistically affect OS or PFS in cancer patients.…”

Changes in high endothelial venules in lymph nodes after vascularized and nonvascularized lymph node transfer in a murine autograft model

“…In contrast, Sasaki et al found that HEVs appeared 10 days after nonvascularized mesenteric LNT with fragmentation, and the regeneration of transplanted LN fragments was structurally complete with normal HEVs on day 28 in a rat autograft model . Using a murine model inoculated with B16F10 melanoma cells, we recently demonstrated that the lumens of HEVs in a nonvascularized autotransplanted PLN were not dilated when compared with those in an intact PLN 6 weeks after surgery in the premetastatic phase …”

“…Using a murine model inoculated with B16F10 melanoma cells, we recently demonstrated the immune‐mediated antitumor effect of nonvascularized LN autotransplantation through activation of T‐cells, showing the expansion of lymphocytes and a change in the lymphocyte population . In that study, the function of the transplanted LN was affected by the change in HEVs brought about by decreased vascularity, so maintaining vascularization may also be important for regeneration of HEVs to maintain the immune functions of the LN. Accordingly, we evaluated the feasibility of pedicled vascularized LNT in a murine model with a postoperative assessment of lymphatic flow using indocyanine green lymphography …”