1.Tumor Microenvironment Polyamines Inhibit T Cell Antitumor Activity
Yuan-Bao AI ; Xue-Mei HUANG ; Sen LIU
Progress in Biochemistry and Biophysics 2025;52(8):1986-1997
Tumor immunotherapy has emerged as the fourth major therapeutic modality, following surgery, radiotherapy, and chemotherapy. Unlike traditional treatments that primarily target tumor cells directly, immunotherapy harnesses the body’s immune system to recognize and eliminate cancer cells. Over the past decade, various immunotherapeutic strategies have been developed, including immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T cell therapy, cancer vaccines, and cytokine-based therapies. However, the immunosuppressive tumor microenvironment (TME) poses a significant obstacle to the effectiveness of these treatments. Polyamines—including putrescine, spermidine, and spermine—are polycationic metabolites that often accumulate abnormally in the TME and act as critical immunoregulatory molecules. T cells play a central role in antitumor immunity, yet their function is frequently influenced by immunoregulatory factors within the TME. Elevated polyamine levels in the TME have been implicated in dampening antitumor T cell responses, thereby facilitating tumor immune evasion. Polyamines in the TME originate from both tumor cells and tumor-associated immune cells. Tumor cells often overexpress the oncogene Myc, which drives the upregulation of polyamine biosynthetic enzymes, resulting in excessive intracellular polyamine production. Additionally, M2-polarized tumor-associated macrophages (M2-TAMs) contribute to polyamine accumulation by upregulating arginase-I (Arg-I), an enzyme that catalyzes the conversion of arginine into ornithine—a key precursor in the polyamine biosynthetic pathway. These combined sources lead to sustained polyamine enrichment in the TME, contributing to immune dysfunction and supporting tumor progression. Moreover, polyamines indirectly affect T cell activity by modulating macrophage polarization and directly suppress tumor cell apoptosis, further promoting an immunosuppressive environment. This review highlights the multifaceted roles of polyamines in modulating tumor-infiltrating T cell function, with a particular focus on their influence on CD4+ T cell differentiation,CD8+ T cell cytotoxicity, and immune checkpoint molecule expression. Recent studies suggest that polyamines suppress CD4+ T cell activation and differentiation by modulating the MAPK/ERK signaling pathway. Additionally, polyamines can impair T cell receptor (TCR) signaling and promote immune evasion through the upregulation of PD-L1 expression on tumor cells. These effects collectively contribute to weakened antitumor T cell responses. Polyamine blocking therapy (PBT), which primarily targets polyamine biosynthesis and transport, has emerged as a novel adjunctive immunotherapeutic strategy in cancer treatment. By reducing polyamine levels in the TME, PBT restores T cell effector functions and alleviates immunosuppression. Notably, studies have demonstrated that combining PBT with ICIs produces synergistic antitumor effects and may overcome resistance to ICI monotherapy. Although research has revealed the inhibitory effects of polyamines on T cell immune function, the underlying regulatory mechanisms remain to be fully elucidated. Moreover, due to compensatory mechanisms employed by tumor cells to maintain polyamine homeostasis, multi-targeted approaches may be necessary to achieve safe and effective therapeutic outcomes. Future PBT strategies may benefit from the integration of multi-omics technologies and the development of nanocarrier-based drug delivery systems, which could collectively enhance their specificity, efficacy, and applicability in cancer immunotherapy. This review systematically elucidates the immunomodulatory effects of polyamines on T cell function within the TME and provides theoretical support and novel insights for the advancement of tumor immunotherapeutic strategies.
2.Triaging patients in the outbreak of COVID-2019
Guo-Qing HUANG ; Wei-Qian ZENG ; Wen-Bo WANG ; Yan-Min SONG ; Xiao-Ye MO ; Jia LI ; Ping WU ; Ruo-Long WANG ; Fang-Yi ZHOU ; Jing WU ; Bin YI ; Zeng XIONG ; Lu ZHOU ; Fan-Qi WANG ; Yang-Jing TIAN ; Wen-Bao HU ; Xia XU ; Kai YUAN ; Xiang-Min LI ; Xin-Jian QIU ; Jian QIU ; Ai-Min WANG
Chinese Journal of Infection Control 2023;22(3):295-303
In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50%of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.
3.Reflections on supervision strategies of new Tibetan drug registration.
Dan LIANG ; Tsring PEMBA ; Jiang-Yong YU ; Jian-Yuan TANG ; Yue-Hua ZHOU ; Hua HUA ; Wei-Wu CHEN ; Yan-Ling AI ; Gang ZHOU ; Lei ZHANG ; Ting WANG ; Yong-Wen ZHANG ; Chong ZOU ; Wei-Xiong LIANG ; Jie-Lai XIA ; Nai-Qing ZHAO ; Xiao-Bo SUN ; Wei WEI ; Bao-He WANG ; Hong DING ; Guo-Chen WANG ; Tsring PUQIONG ; Phuntsok KELSNG ; Guo-Qiang WANG
China Journal of Chinese Materia Medica 2022;47(19):5383-5388
Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
Tibet
;
Medicine, Tibetan Traditional
;
Quality Control
;
Pharmaceutical Research
;
Drug Industry
4.Reverse variant of follicular lymphoma: report of a case.
Yi LIN ; Xiao Jie WANG ; Xiao Li LIU ; Jin BAO ; Xiao Ai CHENG ; Haixia YUAN
Chinese Journal of Pathology 2022;51(11):1177-1179
6.Clinical Characteristics and Bone Marrow Histopathology Features in Essential Thrombocythaemia Patients with Different Gene Mutation in China.
Xiu-Peng YE ; Rong WANG ; Quan-Gui WANG ; Yan WANG ; Jian-Fu ZHANG ; Chun QIAO ; Hong-Juan LIU ; Ke-Danmu Aierken AI ; Xing-Xing CHAI ; Xing-Yu LU ; Xiao-Qing LIU ; Lang CHEN ; Zheng-Yuan LIU ; Ye-Qiong LI ; Chun-Yu ZHANG ; Fang LI ; Guang-Sheng HE ; Shen BAO
Journal of Experimental Hematology 2020;28(4):1326-1331
OBJECTIVE:
To investigate the clinical characteristics, laboratorial and bone marrow pathological features of primary thrombocytopenia (ET) patients with different mutations of CALR, JAK2 and MPL genes.
METHODS:
The chinical data of 120 cases of ET in Jiangsu provincial people's hospital/ The First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2017 were collected and analyzed, including 76 cases with JAK2 gene mutation, 40 cases with CALR gene mutation, 2 cases with MPL gene mutations, 2 cases without gene mutation.
RESULTS:
Among the ET patients, compared with the JAK2 gene mutation, CALR gene mutation showed statistically significant deareament of white blood cells and hemoglobin (P=0.001, P=0.01) and the male platelets in CALR group showed significant increament (P=0.04). Fourthermore, the average number of megakaryocytes and its cluster numbers in each hight power field of vision showed statistically significant decreament in CALR group as compared with JAK2 group (P=0.001, P=0.001), and thrombotic events in CALR group were signicantly lower than those in JAK2 group (7.5% vs 18.4%) (P=0.03).
CONCLUSION
Mutations of CALR, JAK2 have different clinical characteristics and blood pathological changes of Chinese ET patients, and their clinical significance is worth to explore.
Bone Marrow
;
Calreticulin
;
genetics
;
China
;
Humans
;
Janus Kinase 2
;
genetics
;
Male
;
Mutation
;
Receptors, Thrombopoietin
;
genetics
;
Thrombocythemia, Essential
7.Spectrum-effect Relationship of Anti-hepatoma Activity from 3 Kinds of Genus Paris Based on Cluster Analysis and Grey Relational Analysis
Ruo-shi LI ; Hui-qiong YUAN ; Jiang LIU ; Fei-ya ZHAO ; Ai-en TAO ; Bao-zhong DUAN ; Ying WANG ; Cong-long XIA
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(8):192-198
Objective::To study the spectrum-effect relationship between HPLC fingerprints and anti-hepatoma activity of
8.Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial
Wang HONG-XING ; Wang KUN ; Zhang WEN-RUI ; Zhao WEN-FENG ; Yang XIAO-TONG ; Wang LI ; Penn MAN ; Sun ZHI-CHAO ; Xue QING ; Jia YU ; Li NING ; Dong KAI ; Zhang QIAN ; Zhan SHU-QIN ; Min BAO-QUAN ; Fan CHUN-QIU ; Zhou AI-HONG ; Song HAI-QING ; Yin LU ; Si TIAN-MEI ; Huang JING ; Lu JIE ; Leng HAI-XIA ; Ding WEI-JUN ; Liu YUAN ; Yan TIAN-YI ; Wang YU-PING
Chinese Medical Journal 2020;133(1):61-67
Background:Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD).The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week,double-blind,randomized,placebo-controlled study.Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min,77.5-Hz,15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4),following a 4-week observation period (week 8).The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8.Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17,the proportion of participants having improvement in the clinical global impression-improvement,the change in HDRS-17 score (range,0-52,with higher scores indicating more depression) over the study,and variations of brain imaging and neurocognition from baseline to week 4.Safety will be assessed by vital signs at weeks 4 and 8,and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.
9. Determination and Analysis of Heavy Metals of Paridis Rhizoma from Different Localities and Pieces
Ruo-shi LI ; Hui-qiong YUAN ; Fei-ya ZHAO ; Ai-en TAO ; Bao-zhong DUAN ; Kan HU ; Cong-long XIA
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(15):30-36
Objective:To analyze and determine heavy metal content in Paridis Rhizoma from different genus and localities,in order to provide a reference for selecting cultivation areas and establishing the quality standard of Paridis Rhizoma of heavy metals content. Method:Microwave digestion method combined with inductively coupled plasma atomic emission spectrometry method (ICP-AES) method were applied to determine the contents of 6 heavy metals,i.e. As,Cu,Hg,Cd,Pb and Cr in 39 samples of Paridis Rhizoma of different genus and localities in Yunnan Province. Cluster analysis,statistical analysis and principal component analysis (PCA) were used to compare the differences of heavy metals contents in different localities and species. Result:The contents of six heavy metals in Paridis Rhizoma met the ISO international standard of Heavy Metal Limit of Traditional Chinese Medicine-traditional Chinese Medicinal Materials. Under the limited value standard of Green Trade Standards of Importing Medicinal Plants and Preparations,the over-standard rate of heavy metal As was 15.4%,the excess rate of Cd was 5.1%,and the excess rate of Pb was 2.6%. The contents of Cu and Hg conformed to relevant requirements. Cluster analysis,statistical analysis and principal component analysis showed that for the same variety,differences in producing places had significant effects on heavy metal content,while differences in species had little effects. Conclusion:The results of this study indicated that the heavy metal content of Paris planted in and around Dali basically conformed to relevant standards. The differences of heavy metal content in Paris were mainly regional differences,which provided a theoretical basis for standardizing the cultivation of medicinal materials and formulating the limit standards of heavy metals for Paridis Rhizoma.
10.Artificial intelligence system of faster region-based convolutional neural network surpassing senior radiologists in evaluation of metastatic lymph nodes of rectal cancer.
Lei DING ; Guang-Wei LIU ; Bao-Chun ZHAO ; Yun-Peng ZHOU ; Shuai LI ; Zheng-Dong ZHANG ; Yu-Ting GUO ; Ai-Qin LI ; Yun LU ; Hong-Wei YAO ; Wei-Tang YUAN ; Gui-Ying WANG ; Dian-Liang ZHANG ; Lei WANG
Chinese Medical Journal 2019;132(4):379-387
BACKGROUND:
An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use.
METHODS:
Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome; recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model.
RESULTS:
Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients.
CONCLUSION:
Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists.
TRIAL REGISTRATION
www.chictr.org.cn (No. ChiCTR-DDD-17013842).
Adult
;
Aged
;
Aged, 80 and over
;
Artificial Intelligence
;
Female
;
Humans
;
Lymphatic Metastasis
;
Male
;
Middle Aged
;
Neoplasm Recurrence, Local
;
Neoplasm Staging
;
Neural Networks (Computer)
;
Pathologists
;
Radiologists
;
Rectal Neoplasms
;
diagnostic imaging
;
mortality
;
pathology

Result Analysis
Print
Save
E-mail