T helper (Th) cells have received extensive attention owing to their indispensable roles in anti-tumor immune responses. Th1 and Th2 cells are two key subsets of Th cells that exist in relative equilibrium through the secretion of cytokines that suppress their respective immune response. When the type of cytokine in the tumor microenvironment is altered, this equilibrium may be disrupted, leading to a shift from Th1 to Th2 immune response. Th1/Th2 imbalance is one of the decisive factors in the development of malignant tumors. Therefore, focusing on the balance of Th1/Th2 anti-tumor immune responses may enable future breakthroughs in cancer immunotherapy. Polysaccharides can regulate the imbalance between Th1 and Th2 cells and their characteristic cytokine profiles, thereby improving the tumor immune microenvironment. To our knowledge, this study is the most comprehensive assessment of the regulation of the tumor Th1/Th2 balance by polysaccharides. Herein, we systematically summarized the intrinsic molecular mechanisms of polysaccharides in the regulation of Th1 and Th2 cells to provide a new perspective and potential target drugs for improved anti-tumor immunity and delayed tumor progression.

Cryptotanshinone (IUPAC name: (R)-1,2,6,7,8,9-hexahydro-1,6,6-trimethyl-phenanthro(1,2-b)furan-10,11-dione), a biologically active constituent extracted from the roots and rhizomes of the plant Salvia miltiorrhiza, has been studied in depth as a medicinally active compound and shown to have efficacy in the treatment of numerous diseases and disorders. In this review, we describe in detail the current status of cryptotanshinone research, including findings relating to the structure, pharmacokinetics, pharmacological activity, and derivatives of this compound. Cryptotanshinoneh as a diverse range of pharmacological effects, including anti-cancer, anti-inflammatory, immune regulatory, neuroprotective, and anti-fibrosis activities. Studies on the molecular mechanisms underlying the activities of cryptotanshinone have established that the JAK2/STAT3, PI3K/AKT, NF-κB, AMPK, and cell cycle pathways are involved in the inhibitory and pro-apoptotic effects of cryptotanshinone on different tumor cell lines, these molecular pathways interact in a coordinated manner to inhibit cell proliferation, migration and invasion,and induce transformation, autophagy, necrosis, and cellular immunity. The anti-inflammatory mechanisms of cryptotanshinone have been found to be associated with the TLR4-MyD88/PI3K/Nrf2 and TLR4-MyD88/NF-κB/MAPK pathways, whereasthe Hedgehog, NF-κB, and Nrf-2/HO-1 pathways are regulated by cryptotanshinone to reduce organ fibrosis, and its inhibitory effects on the PI3K/AKT-eNOS pathway have been linked to neuroprotective effects. Given the potential medicinal utility of cryptotanshinone, further research is needed to verify the efficacy and safety of this compound in clinical use, evaluate its pharmacological activity, and identify molecular targets.

Innate immune mechanisms initiate immune responses via pattern-recognition receptors (PRRs). Cyclic GMP-AMP synthase (cGAS), a member of the PRRs, senses diverse pathogenic or endogenous DNA and activates innate immune signaling pathways, including the expression of stimulator of interferon genes (STING), type I interferon, and other inflammatory cytokines, which, in turn, instructs the adaptive immune response development. This groundbreaking discovery has rapidly advanced research on host defense, cancer biology, and autoimmune disorders. Since cGAS/STING has enormous potential in eliciting an innate immune response, understanding its functional regulation is critical. As the most widespread and efficient regulatory mode of the cGAS-STING pathway, post-translational modifications (PTMs), such as the covalent linkage of functional groups to amino acid chains, are generally considered a regulatory mechanism for protein destruction or renewal. In this review, we discuss cGAS-STING signaling transduction and its mechanism in related diseases and focus on the current different regulatory modalities of PTMs in the control of the cGAS-STING-triggered innate immune and inflammatory responses.

As one of the most common malignant tumors in humans, lung cancer has experienced a gradual increase in morbidity and mortality. This study examined prognosis-related methylation-driven genes specific to lung adenocarcinoma (LUAD) to provide a basis for prognosis prediction and personalized targeted therapy for LUAD patients. The methylation and survival time data from LUAD patients in the TCGA database were downloaded. The MethylMix algorithm was used to identify the differential methylation status of LUAD and adjacent tissues based on the β-mixture model to obtain disease-related methylation-driven genes. A COX regression model was then used to screen for LUAD prognosis-related methylation-driven genes, and a linear risk model based on five methylation-driven gene expression profiles was constructed. A methylation and gene expression combined survival analysis was performed to further explore the prognostic value of 5 genes independently. There were 118 differentially expressed methylation-driven genes in the LUAD tissues and adjacent tissues. Five of the genes, CCDC181, PLAU, S1PR1, ELF3, and KLHDC9, were used to construct a prognostic risk model. Overall, the survival time was significantly lower in the high-risk group compared with that in the low-risk group (P < 0.05). In addition, the methylation and gene expression combined survival analysis found that the combined expression levels of the genes CCDC181, PLAU, and S1PR1 as well as KLHDC9 alone can be used as independent prognostic markers or drug targets. Our findings provide an important bioinformatic basis and relevant theoretical basis for guiding subsequent LUAD early diagnosis and prognosis assessments.

T cell senescence is an indication of T cell dysfunction. The ability of senescent T cells to respond to cognate antigens is reduced and they are in the late stage of differentiation and proliferation; therefore, they cannot recognize and eliminate tumor cells in a timely and effective manner, leading to the formation of the suppressive tumor microenvironment. Establishing methods to reverse T cell senescence is particularly important for immunotherapy. Aging exacerbates profound changes in the immune system, leading to increased susceptibility to chronic, infectious, and autoimmune diseases. Patients with malignant lung tumors have impaired immune function with a high risk of recurrence, metastasis, and mortality. Immunotherapy based on PD-1, PD-L1, CTLA-4, and other immune checkpoints is promising for treating lung malignancies. However, T cell senescence can lead to low efficacy or unsuccessful treatment results in some immunotherapies. Efficiently blocking and reversing T cell senescence is a key goal of the enhancement of tumor immunotherapy. This study discusses the characteristics, mechanism, and expression of T cell senescence in malignant lung tumors and the treatment strategies.

Immune evasion remains a major obstacle to effective cancer immunotherapy. While the regulatory mechanisms of the tumor biochemical microenvironment are relatively well-characterized, the role of its mechanical microenvironment—particularly pathologically elevated matrix stiffness—in immune evasion remains to be fully elucidated. Immune cells, as dynamic responders within the tumor microenvironment, are not merely passive recipients of mechanical signals but also active participants in driving pathological matrix stiffening. This review focuses on the elevated matrix stiffness resulting from abnormal deposition and crosslinking of the tumor extracellular matrix, systematically elucidating how it impairs immune cell function and drives immune evasion through physical barriers and mechanotransduction. Additionally, we further propose an innovative concept: the "matrix stiffness-immune cell bidirectional regulatory axis." Dissecting this regulatory loop provides an essential mechanical perspective for understanding immune evasion and offers a conceptual framework for developing matrix-targeted strategies to enhance immunotherapy. By integrating current evidence, this review aims to clarify the role of this bidirectional axis and to identify novel therapeutic targets and strategies that may improve the efficacy of cancer immunotherapies.