Fig. 6

illustrates the impact of chemokines on shaping the tumor microenvironment (TME). To begin with, tumor cells release tumor-specific antigens (TAAs) and newly formed antigens designed to be captured and processed by professional antigen-presenting cells (APCs). Conventional dendritic cells (cDCs) undergo maturation and upregulate CCR7, facilitating their migration to lymph nodes that drain the tumor site. The chemotactic axis of CCR7-CCL19/CCL21 guides naïve CD8⁺ and CD4⁺ T cells towards these lymph nodes. Inside the lymph nodes, naïve T cells that recognize TAAs interact with both cDC1s and cDC2s, resulting in activation of CD4⁺ and CD8⁺ T cells, along with increased expression of CXCR3. This directs the activated T cells to specific regions known as interfollicular areas (IFRs) within the lymph nodes. Within the IFRs, CD4⁺ T cells specific to TAAs engage with dendritic cells through CXCR3-dependent mechanisms, promoting their transformation into Th1 cells. Immunological cells with anti-tumor properties, including natural killer (NK) cells, cDC1s, Th1 cells, and CD8⁺ T cells, enter the tumor microenvironment (TME) guided by chemotactic gradients originating from the bloodstream. cDC1s secrete CXCL9 and CXCL10 to attract CXCR3⁺CD8⁺ T cells and enhance the functions of intra-tumoral T effector cells. Activated CD8⁺ T cells and Th1 cells position themselves close to tumor cells to aid in the elimination of tumors either by producing cytokines or directly killing them. Additionally, within the TME, tumor-associated macrophages (TAMs) are attracted to the tumor site as activated monocytes through the chemokine pathways of CCR5-CCL5 and CCR2-CCL2. TAMs promote tumor progression by releasing CCL17, CCL22, and CCL18 to recruit CCR4⁺ and CCR8⁺ regulatory T cells (Treg cells). Interactions between TAMs and tumor cells via the pathways of CCR2-CCL2 and CCR5-CCL5 enhance tumor stemness and metastatic potential. Furthermore, myeloid-derived suppressor cells (MDSCs) and tumor-associated neutrophils (TANs) present in the TME inhibit T cells and NK cells while attracting Treg cells by secreting chemokines such as CCL3, CCL4, CCL5 (by MDSCs), and CCL17 (by TANs). Treg cells are also lured by various chemokine systems, playing a role in tumor growth by suppressing T cell responses within the TME. This figure was created using Figdraw