Topic: Lymph Node Metastasis: Crosstalk Mechanisms and Therapeutic Implications

In cancer therapy, lymph nodes (LNs) have long been recognized both as an "immune battlefield" and as a "metastatic outpost", playing a dual role in tumor progression and antitumor immunity. As the primary site of tumor cell dissemination, LNs serve as the first checkpoint where cancer cells escape from the primary tumor and initiate metastatic colonization; simultaneously, they act as pivotal hubs for activating antitumor immune responses, orchestrating the differentiation and priming of immune cells against tumor antigens.​

The pre-metastatic niche shaped by the tumor immune microenvironment (TIME) provides survival signals, nutrient supply, and a permissive microenvironment for cancer cells to colonize LNs, further facilitating subsequent distant organ metastasis. Conversely, emerging evidence highlights that T cells, the key effectors of successful immunotherapy, predominantly originate from LNs, where naive T cells encounter tumor antigens and differentiate into effector T cells. Notably, certain LN subsets can effectively mount robust antitumor immune responses, underscoring the complex interplay between the lymph node microenvironment and tumor immunity.​

Despite significant advances, the intricate crosstalk mechanisms between the TIME and lymph node metastasis remain largely elusive. To address this knowledge gap, this Special Issue aims to compile cutting-edge research that unravels the molecular and cellular underpinnings of this bidirectional interaction. We welcome submissions focused on the following themes: (1) clinical and basic research investigating how the TIME modulates lymph node metastasis; (2) studies exploring the impact of the lymph node microenvironment on antitumor immune responses; (3) analyses of the microenvironmental characteristics of primary and metastatic tumors to identify molecular targets relevant to lymph node-directed metastasis; and (4) the development of lymph node-targeted immunotherapies or combination therapies informed by the heterogeneity of the lymph node microenvironment. This Special Issue aims to serve as a comprehensive platform for integrating interdisciplinary insights, advancing translational research, and inspiring novel therapeutic strategies targeting lymph node metastasis by harnessing the power of the immune system.

Topics：

1. Clinical and basic research on the regulatory mechanisms of the TIME in lymph node metastasis​;

2. Exploration of the role of the lymph node microenvironment in the initiation and efficacy of antitumor immune responses​;

3. Identification of molecular targets for lymph node-directed metastasis through analyses ofthe microenvironmental characteristics of primary and metastatic tumors;

4. Development of lymph node-targeted immunotherapies and combination therapies based on lymph node microenvironment heterogeneity.

Tumor Immune Microenvironment; Lymph Node Metastasis; Antitumor Immune Response; Lymph Node-targeted Immunotherapy