The tumor microenvironment (TME) represents a complex, dynamic, and heterogeneous system in which stromal and immune elements interact to influence tumor development and mechanisms of immune escape. Within the stromal compartment, cancer-associated fibroblasts (CAFs) have been identified as key mediators of immune regulation in the TME. Emerging evidence indicates that CAFs engage in extensive crosstalk with innate immune cell populations-including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), natural killer (NK) cells, mast cells, and dendritic cells (DCs). Through these interactions, CAFs contribute to the establishment and maintenance of an immunosuppressive milieu that supports tumor progression and facilitates immune evasion. This review summarizes the molecular interactions between CAFs and innate immune cells in the TME. It highlights how CAF-derived factors such as IL-6, TGF-β, CXCL12, and CSF-1 regulate immune cell recruitment and polarization, promoting immunosuppression, tumor progression, angiogenesis, and metastasis. Additionally, feedback signals from immune cells further sustain CAF activation, creating a self-reinforcing immunosuppressive microenvironment. Elucidating these multidirectional interactions offers important insights into tumor biology and identifies promising therapeutic avenues. Targeting CAF-associated signaling pathways or interfering with CAF-immune cell communication may help restore anti-tumor immune responses and improve the effectiveness of cancer immunotherapy strategies.
Colorectal cancer (CRC) is globally ranked as the third leading cause of cancer-related deaths in both men and women. There is an urgent need for novel biomarkers to facilitate early diagnosis and enhance patient care, thereby improving treatment response and reducing mortality rates. Signal transducer and activator of transcription 3 (STAT3) is essential for controlling the anti-tumor immune response since it is a hub for several oncogenic signaling pathways. In the tumor environment, STAT3 is widely overactivated in both malignant and non-cancerous cells. It is involved in suppressing the expression of critical immune activation regulators and encouraging the synthesis of immunosuppressive substances. Long noncoding RNAs (lncRNAs), a kind of non-coding RNA, are critical for CRC development, apoptosis, and metastasis because they influence important signaling pathways such as STAT3 signaling and contribute to gene regulation at the epigenetic, transcriptional, and post-transcriptional levels. Moreover, lncRNAs have a significant role in modifying the TME and control the expression of important immunological checkpoints, such as PD-L1. Therefore, a comprehensive understanding of the regulatory roles of lncRNAs is crucial for identifying diagnostic, prognostic, and predictive biomarkers for CRC. Thus, the objective of the present review study is to provide a comprehensive overview of the interaction between the STAT3 signaling pathway and various lncRNAs, as well as their implications for apoptosis, metastasis, and immune evasion in CRC.
Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.