Immunotherapy has become the fourth cancer therapy after surgery, chemotherapy, and radiotherapy. In particular, immune checkpoint inhibitors are proved to be unprecedentedly in increasing the overall survival rates of patients with refractory cancers, such as advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. However, inhibitor therapies are only effective in a small proportion of patients with problems, such as side effects and high costs. Therefore, doctors urgently need reliable predictive biomarkers for checkpoint inhibitor therapies to choose the optimal therapies. Here, we review the biomarkers that can serve as potential predictors of the outcomes of immune checkpoint inhibitor treatment, including tumor-specific profiles and tumor microenvironment evaluation and other factors.

The clinical trials using immunotherapy have been performed for the treatment of variety of malignant tumors. However, large-scale meta-analysis of combined DC-CTL/CIK therapy on immune and clinical response in patients has not been well studied yet. The purpose of this study is to investigate the role of DC-CTL/CIK therapy and evaluate the changes of immune indicators and tumor serological markers both at an individual level and at a system level, which is an important basis for immunotherapy as well as prognosis estimation. Three cohorts were designed to estimate therapeutic effects on patients with malignant tumors. Tumor serological markers were detected pre- and post-treatment by immunoradiometric methods using commercially available diagnostic kits. Lymphocyte subsets were identified by flow cytometry. The quality of life was assessed by EORTC QLQ-C30 questionnaire. In this study, we found out that Tregs was significantly reduced after transfusion of DC-CTL/CIK cells companied by decreasing serological tumor markers including AFP, CA199 and CA242 in primary liver cancer and CA724 in gastric cancer. A system-level analysis showed that lower percentages of Tregs were detected in patients with long-lasting courses of immunotherapy. Strikingly, a tumor progression indicator, myeloid-derived suppressor cells (MDSC), was dramatically decreased in patients after DC-CTL/CIK treatment. These results suggested that DC-CTL/CIK therapy improves immune functions and the quality of life post-treatment versus pre-therapy, indicating that DC-CTL/CIK therapy might block the deterioration of invasive cancers in these patients. This study demonstrated that DC-CTL/CIK therapy could reduce Tregs, MDSCs, and several crucial serological tumor markers in particular tumors, and improve the function of T cells immune systems and the quality of life in patients with malignant tumor.

Natural killer (NK) cell‑based immunotherapy has emerged as a transformative approach for cancer treatment However, its widespread clinical application faces several challenges, such as donor variability, limited scalability and functional heterogeneity of primary NK cells. Additionally, issues including in vivo persistence, resistance to tumor microenvironment and safety concerns related to genomic instability further hinder its clinical application. Induced pluripotent stem cell (iPSC)‑derived NK cells offer a promising solution. They provide high homogeneity and quality control, genetic engineering flexibility and inexhaustible cell source. This present review highlighted the unique advantages of iPSC‑ NK cells, including clonal uniformity, enhanced cytotoxicity and suitability for large‑scale production, positioning them as an ideal ‘off‑the‑shelf’ therapeutic platform. It discussed the biological properties of iPSC‑derived NK cells, advances in differentiation protocols and strategies to augment their anti‑tumor efficacy through genetic engineering, such as chimeric antigen receptor integration and cytokine optimization. Despite these advantages, several challenges remain, including the need to optimize differentiation efficiency, ensure the safety of gene editing (such as off‑target effects) and improve the in vivo migration and infiltration abilities. With technological advances and clinical validation, this present review aimed to guide future research toward overcoming these barriers to clinical implementation. Ultimately, it is expected that iPSC‑NK will become a core means of next‑generation immunotherapy, promoting the combination of personalized and inclusive cancer treatment.

The extension of human lifespan has intensified the demand for developing more effective strategies to enhance quality of life. Age-related physiological decline and associated diseases now constitute significant societal challenges. As scientific understanding of aging mechanisms deepens, targeted intervention in the aging process is becoming increasingly feasible. Emerging evidence suggests that lifespan extension with preserved healthspan can be achieved through metabolic modulation and innovative molecular biology approaches. Notably, cell-based therapies demonstrate substantial anti-aging potential via multiple mechanisms including metabolic reprogramming, cellular repair systems, tissue regeneration, senescent cell clearance, and immunomodulation. This has catalyzed the emergence of cellular rejuvenation as a distinct discipline within anti-aging research. This review systematically examines current understanding of aging mechanisms, recent advancements in stem cell/immune cell technologies, and their clinical translation in age-related interventions. We further identify key challenges and future directions in the field, aiming to provide novel insights for extending human healthspan and improving geriatric care.

Chimeric antigen receptor T (CAR-T) therapy holds promise for cancer treatment but faces challenges with using fresh patient cells, including manufacturing failures and logistical hurdles. Cryopreserved peripheral blood mononuclear cells (PBMCs) offer a potential solution, and while lentiviral processes have been reported for generating CAR-T from these cells, few studies have demonstrated successful PiggyBac electroporation methods. Therefore, the objectives of our study were twofold: Firstly, to conduct a comparative study on cryopreserved PBMCs, fresh PBMCs, and their respective preparations of CAR-T. Secondly, to establish a PiggyBac electroporation CAR-T preparation process using cryopreserved PBMCs through process optimization. The results revealed that long-term frozen PBMCs viability in a relatively stable manner. CAR-T generated from cryopreserved PBMCs exhibited comparable expansion potential, cell phenotype, differentiation profiles, exhaustion markers, and cytotoxicity against human ovarian cancer cell line (SKOV-3) cells to those derived from fresh PBMCs. Moreover, through process optimization, we further enhanced the proliferation and toxicity of CAR-T. This approach has the potential to revolutionize the CAR-T production model by utilizing healthy donor cells instead of patient cells. This shift could mitigate issues affecting treatment efficacy, such as suboptimal cell condition following illness or delays in cell preparation.

Brain tumours are in the spotlight of oncology research due to their intractability and resistance to conventional treatments. High‑risk craniotomies must be performed on patients during tumour resection surgeries due to the specificity of the brain structure, and the complexity of the brain structure also leads to the fact that brain tumours usually cannot be removed completely. Besides, the inability of foreign small molecules to cross the blood‑brain barrier has led to the inability of conventional drug therapy to reach the tumour location in the brain. Furthermore, the damage to healthy brain tissue caused by conventional radiotherapy cannot be ignored. Therefore, brain tumours represented by gliomas are in urgent need for a novel therapeutic approach. Glioma is the most common brain tumour, accounting for 81% of malignant tumours in the central nervous system, and is characterized by high morbidity, recurrence, mortality and low cure rate. In recent years, natural killer (NK) cell immunotherapy for gliomas has gradually emerged and numerous studies have shown surprising therapeutic effects. NK cells have been demonstrated to traverse the blood‑brain barrier and numerous studies have confirmed their ability to kill glioma cells both in vivo and in vitro. This article begins by introducing conventional therapies for glioma, followed by an overview of the potential of NK cell‑based immunotherapy in glioma treatment and the regulatory mechanisms of NK cells within the glioma immune microenvironment. It then summarizes preclinical studies on CAR‑NK cells and clinical advancements in NK cell therapy for glioma. Finally, the paper discusses recent progress in immunotherapy for gliomas and explores novel therapeutic strategies combining NK cell immunotherapy with other treatment modalities.