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CAR-T cells, which are genetically programmed to specifically recognize and kill target cells, have altered the therapeutic landscape of lymphoma. After the tumor antigens are identified by scFv, CAR-T cells execute anti-tumor activity through granzyme and perforin secretion, inducing cell apoptosis in a Fas-FasL-dependent pathway and producing inflammatory cytokines to antagonize the immunosuppressive tumor microenvironments (TME) and induce host immune responses. However, CAR-T cell therapy still faces many challenges owing to the heterogeneity of tumor cells, interference from TME, T cell exhaustion, as well as severe adverse events. Recent years, advances in tumor immunology and genetic engineering have driven CAR evolution. These new generations of CARs armed with diverse molecular weapons have made significant progress in enhancing the accuracy of recognition, stimulating endogenous immune responses, strengthening killing activity, resisting TME and exhaustion, and improving safety and flexibility, thus gradually overcoming the limitations of CAR-T cell therapy. This review focuses on the advancements of CAR-T cells in the treatment of lymphoma, summarizes the newly emerged modification strategies of CAR, and elucidates their potential prospects.
A team of researchers from the Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, published a review (DOI: 10.20892/j.issn.2095-3941.2024.0538) in Cancer Biology & Medicine. This paper analyzes the mechanisms of various CAR-T modification strategies in counteracting tumor immune escape and TME, while detailing the structures and functions of novel CAR-T designs. Multi-target CAR-T combats antigen loss, TRUCKs enhance cytotoxic activity and stimulate host immune responses through cytokine delivery, and immune checkpoint-switching receptor converts inhibitory signals into immune-activating stimuli to overcome TME-induced exhaustion. Beyond clinically established CAR-T therapies, the review also emphasizes the roles of universal CAR-T (including iPSC-derived, autologous, and in vivo-generated CAR-T), epigenetics, and metabolism. Notably, glycolysis, oxidative phosphorylation, histone acetylation, and DNA methylation interact in a tightly regulated network to influence CAR-T cell phenotype and exhaustion, ultimately shaping systemic antitumor immunity.
Collectively, superior CAR-T cells are expected to have accurate identification, strong killing ability, stability and persistence, high security and flexibility, and easier accessibility. More sophisticated modifications mean greater operational difficulties and higher genetic risks. There may be contradictions among a variety of strategies, and we need to find a balance between the efficacy and memory, lethality and safety.
This work was supported by grants from the Science Technology Department of Zhejiang Province (Grant No. 2021C03117), Noncommunicable Chronic Diseases-National Science and Technology Major Project (Grant No. 2023ZD0501300), National Natural Science Foundation of China (Grant No. 82170219), and Zhejiang Provincial Natural Science Foundation of China (Grant No. LQ24H080009).
About Cancer Biology & Medicine
Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 8.4, 5 year IF 6.7), with all full texts freely visible to clinicians and researchers all over the world (http://www.ncbi.nlm.nih.gov/pmc/journals/2000/).
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Tsukuba, Japan—Displaced aggression, such as lashing out at an unrelated individual after a frustrating experience, is a well-documented phenomenon in both humans and animals. In mice, males typically attack unfamiliar, potentially rival males that enter their territory. However, when the rival was placed inside a transparent enclosure, physical contact was blocked despite visual and olfactory access. This situation increased arousal in the subject—a phenomenon known as "social instigation"—which primed the animal for heightened aggression. When subsequently presented with access to a different rival, the subject exhibited significantly ...
1. Prediction of key genes in the AICAR biosynthetic pathway of endophytic Fusarium solani
Previous study showed that overexpression of the global regulator VeA mediated a significant increase in the antitumor activity of F. solani, with a marked enrichment of differential metabolites including AICAR. To elucidate the molecular regulatory mechanism by which veAOE14 contributed to the increased synthesis of AICAR, we obtained the predicted synthetic pathway of AICAR in F. solani by analyzing the veAOE14 transcriptome and metabolome data, with a total of 10 steps in the major synthetic reactions. Based on the previous findings and predicted ...
A low FODMAP diet developed by Monash University researchers for irritable bowel syndrome (IBS) has been shown to improve gastrointestinal symptoms in women with endometriosis.
Sixty percent of study participants responded to the Low FODMAP Diet (LFD), compared to 26 per cent who responded to a control diet based on Australian Dietary Guidelines.
The majority of those on the LFD experienced a clinically significant improvement in gastrointestinal symptoms, and overall symptom severity was 40 per cent lower on the LFD than on the control diet.
Published in Alimentary Pharmacology and Therapeutics, researchers found that the LFD also eased abdominal pain and bloating, and normalised ...
(Santa Barbara, Calif.) — A condition long considered to be unfavorable to electrical conduction in semiconductor materials may actually be beneficial in 2D semiconductors, according to new findings by UC Santa Barbara researchers published in the journal Physical Review Letters.
Electron-phonon interactions — collisions between charge-carrying electrons and heat-carrying vibrations in the atomic lattice of the material — are considered the primary cause of electrons slowing down as they travel through semiconductor material. But according to UCSB mechanical engineers Bolin Liao and Yujie Quan, when electrons ...
Long-term exposure to wildfire smoke may increase the risk of heart failure (HF), especially in older adults, women and vulnerable populations, according to a study published today in JACC, the flagship journal of the American College of Cardiology. In this first national, population-based study to examine how prolonged wildfire smoke exposure impacts HF risk, compared to other types of air pollution, researchers found that as the level of air pollution from wildfire smoke increased over a two-year period, the risk of developing heart failure ...
In 2025, love and politics are colliding for many LGBTQ+ singles. A new Kinsey Institute and DatingNews survey finds 1 in 4 are changing how they date amid the political climate. The State of Us: National Study on Modern Love & Dating in 2025 shows politics are affecting LGBTQ+ singles across demographics, however Gen Z ages 18-25 are feeling the most impact.
Among the overall sample of 302 respondents:
25% of LGBTQ+ singles say politics have changed how they date
35% of LGBTQ+ adults say they don’t feel safe being open about their identity while dating
18% of respondents said they are taking extra measures to protect their identity and privacy ...
**Various Embargoes**
THE LANCET JOURNALS: Papers being presented at the American Diabetes Association [ADA] 85th Scientific Sessions
The following papers published across The Lancet Group will be presented at the American Diabetes Association [ADA] 85th Scientific Sessions. The conference will take place from Friday 20 June through Monday 23 June 2025 in Chicago, Illinois, USA.
Contact details for corresponding authors are provided should you wish to arrange an interview with the authors. Funding information is listed on ...
Restaurants and dinner hosts could improve dining experiences and reduce social awkwardness by serving guests at the same time, a new study has found.
We have all faced that situation in a restaurant or at a dinner party: our food has arrived but we find ourselves waiting for others at the table to be served before starting. This long-established norm is the subject of new research co-authored by Bayes Business School, that shows we are more concerned about violating this practice ourselves than we are about others doing so.
WATCH: Authors of the study explain its outcomes
The ...
Despite decades of ocean exploration, humans still lack basic answers to one of the most fundamental ecological questions: where is marine life found, and why?
A new study published in Communications Earth & Environment, highlights just how uneven our knowledge of ocean biodiversity really is.
By systematically processing nearly 19 million records from the Ocean Biodiversity Information System (OBIS), the study reveals that global marine biodiversity data from below 30m are heavily biased towards shallow waters (50% of benthic records come from just the shallowest 1% of the ...
Penn-led researchers have turned a deadly fungus into a potent cancer-fighting compound. After isolating a new class of molecules from Aspergillus flavus, a toxic crop fungus linked to deaths in the excavations of ancient tombs, the researchers modified the chemicals and tested them against leukemia cells. The result? A promising cancer-killing compound that rivals FDA-approved drugs and opens up new frontiers in the discovery of more fungal medicines.
“Fungi gave us penicillin,” says Sherry Gao, ...
