Regulatory T cell (Tregs) predominantly maintain the immune balance and prevent autoimmunity via their immunosuppressive functions. However, tumor-infiltrating Tregs (TI-Tregs) may mediate tumor immune tolerance in complex tumor microenvironments, resulting in poor prognosis. Distinguishing specific TI-Treg subpopulations from peripheral Tregs and intratumoral conventional T cells (Tconvs) has recently emerged as an important topic in antitumor therapy. In this review, we summarize novel therapeutic approaches targeting both the metabolic pathways and hallmarks of TI-Tregs in preclinical and clinical studies. Although the phenotypic and functional diversity of TI-Tregs remains unclear, our review provides new insights into TI-Treg-based therapies and facilitates precision medicine for tumor treatment.
Humans ; Tumor Microenvironment/immunology* ; T-Lymphocytes, Regulatory/immunology* ; Neoplasms/therapy* ; Animals ; Lymphocytes, Tumor-Infiltrating/metabolism*

Chimeric antigen receptor-T (CAR-T) cell therapy, as a novel cellular immunotherapy, has dramatically reshaped the landscape of cancer treatment, especially in hematological malignancies. However, relapse is still one of the most troublesome obstacles to achieving broad clinical application. The intrinsic factors and superior adaptability of tumor cells mark a fundamental aspect of relapse. The unique biological function of CAR-T cells governed by their special CAR construction also affects treatment efficacy. Moreover, complex cross-interactions among CAR-T cells, tumor cells, and the tumor microenvironment (TME) profoundly influence clinical outcomes concerning CAR-T cell function and persistence. Therefore, in this review, based on the most recent discoveries, we focus on the challenges of relapse after CAR-T cell therapy in B-cell malignancies from the perspective of tumor cells, CAR-T cells, and the TME. We also discuss the corresponding basic and clinical approaches that may overcome the problem in the future. We aim to provide a comprehensive understanding for scientists and physicians that will help improve research and clinical practice.
Cell- and Tissue-Based Therapy ; Humans ; Immunotherapy, Adoptive/methods* ; Neoplasm Recurrence, Local/therapy* ; Neoplasms/pathology* ; Receptors, Chimeric Antigen ; T-Lymphocytes ; Tumor Microenvironment

Objective To study the clinical and prognostic value of CK19 mRNA-positive circulating tumor cells in early breast cancer patients. Methods We analyzed the peripheral blood in 50 patients with early breast cancer after surgery and before the initiation of any adjuvant treatment for the presence of CK19 mRNA-positive circulating tumor cells using a nest reverse polymerase chain reaction assay. All patients were followed up. Results CK19 mRNA-positive cells were detected in 40.0 %(20/50) of patients with early breast cancer, 12.5 %(3/24) of patients with breast benign lesions, but 5 %(1/20) in healthy individuals (P =0.017,P =0.004); 11 to 20 of them relapsed during the follow-up period (P =0.002). There was no significant association between the detection of CK19 mRNA-positive cell and the patients' menstrual status, tumor stage, tumor size, etc (P ＞0.05). Detection of peripheral-blood CK19 mRNA-positive cells was associated with reduced median relapse-free interval in early breast cancer patients (P =0.007). Conclusion CK19 mRNA is one of the molecular markers for the detection of circulating tumor cells in early breast cancer. Detection of peripheral blood CK19 mRNA-positive cells might be an important predictive value as a marker of relapse in early breast cancer patients.