While programmed cell death ligand 1 (PD-L1) inhibitors have yielded breakthroughs in tumor therapy, their efficacy is constrained by the heterogeneity of the tumor microenvironment and multiple immunosuppressive pathways. In recent years, research has revealed that transforming growth factor-β (TGF-β) synergistically drives tumor cell immune escape with PD-L1 via pathways such as metabolic reprogramming, epithelial-mesenchymal transition, and SOX family factors. Currently, various PD-L1/TGF-β bispecific antibodies (bsAbs) have exhibited promising therapeutic potential in early-phase clinical trials, yet they still confront challenges related to toxicity and drug resistance. This article systematically reviews the mechanisms by which PD-L1 and TGF-β synergistically regulate tumor immune escape, summarizes the clinical research progress of bsAbs, and discusses strategies for novel drug design and biomarker development, with the aim of offering new insights for the development of combined tumor immunotherapy strategies.

Cancer-associated fibroblasts (CAFs) are core regulators in the tumor microenvironment. Their high heterogeneity and plasticity remarkably influence the infiltration and function of CD8+ T cells, thereby determining the response to immunotherapy. However, the mechanisms by which CAFs impede CD8+ T cell infiltration exhibit substantial heterogeneity across different cancer types. This review proposes a dichotomous model of CAFs-mediated immune exclusion: Type Ⅰ active exclusion (exemplified by pancreatic ductal adenocarcinoma, where CAFs create physical and chemical barriers through excessive extracellular matrix deposition and secretion of TGF-β/CXCL12) and Type Ⅱ immune ignorance (exemplified by a subset of microsatellite-stable colorectal cancers, where loss of CAFs function results in insufficient chemokine production). Under this framework, we systematically review the specific regulatory mechanisms of CAFs subsets, specifically myofibroblastic CAFs and inflammatory CAFs, in pancreatic cancer, triple-negative breast cancer, non-small cell lung cancer, and colorectal cancer, highlighting their multidimensional roles in extracellular matrix remodeling, metabolic reprogramming, and construction of immunosuppressive networks. Furthermore, by integrating single-cell and spatial multi-omics perspectives, we propose immune phenotype-based CAFs-targeting strategies, namely, "barrier-breaking" strategies (TGF-β inhibition and FAP targeting) for Type Ⅰ tumors and "activating" strategies (reprogramming CAFs toward an immune-supportive phenotype) for Type Ⅱ tumors, and discuss their temporally sequenced combination with immune checkpoint inhibitors.

【Objective】 To analyze the correlation between the expressions of ZEB1, androgen receptor (AR), E-cadherin (E-Ca), N-cadherin (N-Ca) and clinicopathological features of prostate cancer patients with different risk levels, and to explore their significance. 【Methods】 The clinical data of 47 patients with prostate cancer treated during Nov.2013 and Jun.2021 were retrospectively analzyed. The patients were divided into medium-low risk group and high-risk group. The expressions of ZEB1, AR, E-Ca and N-Ca in the prostate cancer tissues of the two groups were detected with immunohistochemical staining. The relationship between the expressions and Gleason grade, prostate-specific antigen (PSA) level and TNM stage was analyzed. 【Results】 The positive expression rate of ZEB1 increased with higher risk, Gleason score, and PSA level (P<0.01); the strong positive expression rate of AR decreased with higher risk and Gleason score (P<0.05); the positive expression rate of E-Ca decreased with increased risk, Gleason score, and PSA level (P<0.05); the positive expression rate of N-Ca increased with the increased risk and Gleason score (P<0.01); the positive expression rate of ZEB1 increased with higher tumor stage and TNM stage (all P<0.01); the strong positive expression rate of AR decreased only with increased TNM stage (P<0.05). Patients whose first surgical specimen showing a higher expression level of ZEB1 were more likely to develop into castration-resistant prostate cancer CRPC (P<0.05). 【Conclusion】 ZEB1 and N-Ca levels increase with increased tumor aggressiveness, while AR and E-Ca levels decrease. ZEB1, AR, E-Ca and N-Ca play important roles in prostate cancer progression. ZEB1 can not only affect prostate cancer through epithelial stromal transformation (EMT), but also through AR. ZEB1 may also be related to the development of CRPC.