Abstract
The complex tumor microenvironment (TME) plays a vital role in cancer development and dramatically determines the efficacy of immunotherapy. Tertiary lymphoid structures (TLSs) within the TME are well recognized and consist of T cell-rich areas containing dendritic cells (DCs) and B cell-rich areas containing germinal centers (GCs). Accumulating research has indicated that there is a close association between tumor-associated TLSs and favorable clinical outcomes in most types of cancers, though a minority of studies have reported an association between TLSs and a poor prognosis. Overall, the double-edged sword role of TLSs in the TME and potential mechanisms need to be further investigated, which will provide novel therapeutic perspectives for antitumor immunoregulation. In this review, we focus on discussing the main functions of TLSs in the TME and recent advances in the therapeutic manipulation of TLSs through multiple strategies to enhance local antitumor immunity.
Highlights
Tumors originate and develop in a complicated and dynamic microenvironment, and there are endothelial cells, immune cells, and stromal cells existing around or within the tumor microenvironment (TME) and interacting with tumor cells [1, 2]
These findings show that the CCL19/CCL21-CCR7 and CXCL13CXCR5 axes are vital for regulating tertiary lymphoid structures (TLSs) development [49]
This study showed that CD8+ tumor-infiltrating lymphocytes (TILs) can predict prognosis only in combination with plasma cells (PCs), CD20+ TILs, and CD4+ TILs, suggesting that these four lymphocyte subsets work in concert to promote antitumor immunity, which indicates that TLSs may facilitate coordinated antitumor responses involving the combined actions of cytolytic T cells and PCs [58]
Summary
Double-Edged Sword Role in Antitumor Immunity and Potential Therapeutic Induction Strategies. The complex tumor microenvironment (TME) plays a vital role in cancer development and dramatically determines the efficacy of immunotherapy. Tertiary lymphoid structures (TLSs) within the TME are well recognized and consist of T cell-rich areas containing dendritic cells (DCs) and B cell-rich areas containing germinal centers (GCs). The double-edged sword role of TLSs in the TME and potential mechanisms need to be further investigated, which will provide novel therapeutic perspectives for antitumor immunoregulation. We focus on discussing the main functions of TLSs in the TME and recent advances in the therapeutic manipulation of TLSs through multiple strategies to enhance local antitumor immunity
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