COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

The Effect of BCG-PSN on T-cell Subsets and Cytokines in Vernal Conjunctivitis

The effects of BCG PSN on T cell subsets and cytokines in vernal conjunctivitis were observed. The level of total IgE was quantitatively determined before and after treatment with BCG PSN by allergen diagnostic instrument in vitro . The content of T cell subsets of peripheral blood and cytokine were determined by using indirect immune fluorescence method, and IL 4 and INF γ were quantified by ELISA. The results showed that the level of total IgE was substantially reduced ( P <0.01) after treatment in the BCG PSN group. Meanwhile, CD + 8 was decreased, CD + 4 and CD + 4/CD + 8 ratio elevated with significant differences ( P <0.05) as compared with pre treatment results. The changes in total IgE, CD + 8 ,CD + 4 and CD + 4/CD + 8 ratio after treatment also presented significant differences ( P <0.05) between BCG PSN group and routine treatment group. The level of IL 4 in serum declined ( P <0.05) after treatment in the BCG PSN group, and INF γ went up ( P <0 05). IL 4 and INF γ in serum showed significant differences ( P <0.05) between two groups after treatment. It is concluded that BCG PSN has a bi directional immunoregulating effect. It can bring CD + 4 and CD + 8 into homeostasis, thereby preventing the occurrence of anaphylaxis. At the same time, BCG PSN can restrain Th 2, decrease the synthesis of IL 4, switch the balance of Th l/Th 2 to Th 1 side, boost up the predominance of Th 1 relatively, which is propitious to perennial stabilization and recovery of vernal conjunctivitis.

Effect of Methionine Deficiency on the Thymus and the Subsets and Proliferation of Peripheral Blood T-Cell,and Serum IL-2 Contents in Broilers

The purpose of this study was to investigate the effects of methionine deficiency on cellular immune function by determining morphological and ultrastructural changes of thymus, thymic cell cycle and apoptosis, peripheral blood T-cell subsets, T- cell proliferation function and the serum interleukin-2 （IL-2） contents. 120 1-d-old broilers were randomly divided into two groups （6 replicates in each group and l0 broilers in each replicate） and fed on a control diet or methionine deficient diet for 42 d. Lesions were observed in experiment. Histopathologically, lymphopenia and congestion were observed in the medulla of thymic lobule. Ultrastructurally, there were more apoptosis lymphocytes, and the mitochondria of lymphocytes were swelled in thymus of methionine deficiency. The G0/G~ phase of the cell cycle of the thymus was much higher （P〈0.01）, and the S, G2＋M phases and proliferating index （PI） were lower （P〈0.01） in methionine deficiency than in control group. And the percentage of apoptotic cells in the thymus was significantly increased in methionine deficiency （P〈0.01）. The percentage of CD4＋ and CD8~ T-cells was decreased in methionine deficiency compared with control group. Meanwhile, the proliferation function of peripheral blood T-cell was decreased in methionine deficiency. Also, the serum IL-2 contents were decreased in methionine deficiency. It was concluded that methionine deficiency could cause pathological and ultrastructural changes of thymus, reduce the T-cell population, serum IL-2 contents and the proliferation function of T- cells, and induce increased percentage of apoptotic cells. The cellular immune function was finally impaired in broilers.

Cross-talk between T-cells and gut-microbiota in neurodegenerative disorders

The emerging role of gut microbiota as a key player in the development of neurodegenerative disorders: Mammals have evolved together with commensal microbiota to establish a symbiotic relationship in which they regulate reciprocally by synthesizing and responding to several common chemical substances. In this regard, gut microbiota constitutes a consortium of bacteria that not only participates in the degradation of nutrients, but also produces metabolites, fatty acids and neurotransmitters that can act on the enzymes and receptors expressed in eukaryotic cells, which considerably affects the physiology of the host and contribute to maintaining homeostasis (Lyte, 2013).

Qingyi decoction attenuates intestinal epithelial cell injury via the calcineurin/nuclear factor of activated T-cells pathway

BACKGROUND Recent studies have demonstrated that dysfunction of the intestinal barrier is a significant contributing factor to the development of severe acute pancreatitis(SAP).A stable intestinal mucosa barrier functions as a major anatomic and functional barrier,owing to the balance between intestinal epithelial cell(IEC)proliferation and apoptosis.There is some evidence that calcium overload may trigger IEC apoptosis and that calcineurin(CaN)/nuclear factor of activated Tcells(NFAT)signaling might play an important role in calcium-mediated apoptosis.AIM To investigate the potential mechanisms underlying the therapeutic effect of Qingyi decoction(QYD)in SAP.METHODS A rat model of SAP was created via retrograde infusion of sodium deoxycholate.Serum levels of amylase,tumor necrosis factor(TNF-α),interleukin(IL)-6,D-lactic acid,and diamine oxidase(DAO);histological changes;and apoptosis of IECs were examined in rats with or without QYD treatment.The expression of the two subunits of CaN and NFAT in intestinal tissue was measured via quantitative realtime polymerase chain reaction and western blotting.For in vitro studies,Caco-2 cells were treated with lipopolysaccharide(LPS)and QYD serum,and then cell viability and intracellular calcium levels were detected.RESULTS Retrograde infusion of sodium deoxycholate increased the severity of pancreatic and intestinal pathology and the levels of serum amylase,TNF-α,and IL-6.Both the indicators of intestinal mucosa damage(D-lactic acid and DAO)and the levels of IEC apoptosis were elevated in the SAP group.QYD treatment reduced the serum levels of amylase,TNF-α,IL-6,D-lactic acid,and DAO and attenuated the histological findings.IEC apoptosis associated with SAP was ameliorated under QYD treatment.In addition,the protein expression levels of the two subunits of CaN were remarkably elevated in the SAP group,and the NFATc3 gene was significantly upregulated at both the transcript and protein levels in the SAP group compared with the control group.QYD significantly restrained CaN and NFATc3 gene expression in the intestine,which was upregulated in the SAP group.Furthermore,QYD serum significantly decreased the LPS-induced elevation in intracellular free Ca^(2+)levels and inhibited cell death.CONCLUSION QYD can exert protective effects against intestinal mucosa damage caused by SAP and the protective effects are mediated,at least partially,by restraining IEC apoptosis via the CaN/NFATc3 pathway.

T-CELL SUBSETS OF PERIPHERAL BLOOD AND SPLEEN IN HEPATOCARCINOMA-BEARING RATS

T-cell subsets from peripheral blood and spleen were investigated prospectively by flow cytometry in a murine intrahepatic implanted tumor model. Peripheral blood OX-19+ cells (pan T-cells) and W3/25+ cells (Th cells) decreased with tumor development in tumor-bearing rats, giving significant differences when compared with healthy rats. No significant changes were found in OX-8+ cells (Ts cells). Hence, Th Ts ratio in tumor-bearing rats was lower than that in control group. Meanwhile, on day 17 following tumor implantation, in tumor-bearing rats with intrahepatic or peritoneal metastasis, there were less W3/25+ cells and more OX-8+ cells than those of hepatoma-bearing rats without metastasis (p<0.01). In the spleen, the phenotypes of lymphocyte markers showed less OX-8+ cells and more OX-12+ cells (B cells) tumor-bearing rats. It was suggested that, in tumor-bearing host, not only was T-cell immune function inhibited, but also there was abnormal distribution of T-cell subsets. It seems that there is a close relationship between tumor growth and its spread and a lower Th/Ts ratio.

Tumor Antigen Specific Activation of Primary Human T-Cells Expressing a Virally Encoded Chimeric T-Cell Receptor Specific for p185HER2

We have developed and tested chimeric T-cell receptors (TCR) specific for p185HER2. In these experiments, retroviral vectors expressing the N29γ or N29ζ receptors were constructed in pRET6. Amphotropic viral producer cells were established in the GALV-based PG13 packaging cell line. Ficoll purified human peripheral blood lymphocytes (PBL) were virally transduced using an optimized protocol incorporating activation with immobilized anti-CD3/anti-CD28 monoclonal anti- bodies, followed by viral infection in the presence of fibronectin fragment CH296. Transduced cells were co-cultured with human tumor cell lines that overexpress (SK-OV-3) or underexpress (MCF7) p185HER2 to assay for antigen specific im- mune responses. Both CM+ and CD8+ T-cells transduced with the N29γ or N29ζ chTCR demonstrated HER2-specific anti- gen responses, as determined by release of Th1 like cytokines, and cellular cytotoxicity assays. Our results support the fea- sibility of adoptive immunotherapy with genetically modified T-cells expressing a chTCR specific for p185HER2.

ICAM-1 depletion in the center of immunological synapses is important for calcium releasing in T-cells

T-cell activation requires the formation of the immunological sy napse(IS)bet ween a T-cll and anantigen-presenting cell(AP C)to control the development of the adaptive immune response.How-ever,calcium release,an initial signal of T-cell activation,has been found to occur before IS for-mation.The mechanism for triggering the calcium signaling and relationship bet ween calciumrelease and IS format ion remains unclear.Herein,using live-cell imaging,we found that int ercellularadhesion molecule 1(ICAM-1),an essential mdlecule for IS formation,accumulated and then wasdepleted at the center of the synapse before complete IS formation.During the proces of ICAM1depletion,calcium was released.if ICAM-1 failed to be depleted from the center of the synapse,thesustained calcium signaling could not be induced.Moreover,depletion of ICAM-1 in ISs preferen-tially ccurred with the contact of antigen-specific T-cels and dendritic clls(DCs).Blocking thebinding ofICA M-1 and lymphocy te finction-associated antigen 1(LFA-1),ICAM-1 failed to depleteat the center of the synapse,and calcium release in T-clls decreased.In studying the mechanism ofhow the depletion ofiCA M1 could influence calcium release in T-clls,we found that the movementof ICAM-1 was associat ed with the localization of LFA-1 in the IS,which afected the localization ofcalcium microdomains,ORAIl and mitochondria in IS.Therefore,the depletion of ICAM-1 in the center of the synapse is an important factor for an initial sust ained calcium release in T-cells.

Effects of the Novel Anti-Asthenic Drug Ladasten on Behavior and T-Cell Subsets Alterations in a Social Defeat Animal Model of Depression

The aim of the present study was to investigate the effects of the anti-asthenic drug ladasten on behavioral patterns and T-cell subsets in blood, spleen, and thymus in socially stressed male C57Bl/6 mice. Mice subjected to social defeat stress (SDS) for 25 days developed a depressive-like phenotype. The submissive SDS animals were assigned to one of two treatment groups: one group was treated with ladasten (30 mg/kg, i.p.) for up to 5 days, and the other one was administered vehicle as a control. Twenty four hours after the last injection, behavioral parameters were tested, and trunk blood and tissue samples were collected. SDS mice from the vehicle-treated group showed a subordinate and passive avoidance behavior with significantly decreased spontaneous locomotor activity (SLA) and exhibited impaired parameters in the forced swimming test (FST). Changes in behavioral status were correlated with an increase spleen weight, a decrease in thymic index and a shift in the CD4/CD8 balance toward T-cytotoxic cells. The behavior parameters were reversed in the group treated with ladasten compared to the untreated SDS group and were similar to those of unstressed mice. Treatment of socially stressed mice with ladasten normalized the amount of T-lymphocyte cells in the blood, spleen, and thymus. These findings support the notion that depression is accompanied by cell-mediated immune activation and that targeting this pathway may be a new therapeutic approach for treatment. Furthermore, our data support further investigations of ladasten as a potent anti-depressive drug which can be used alone as well as in combination with other anti-depressants.

Cytotoxic T-cells as imaging probes for detecting glioma

Tumor vaccination using tumor-associated antigenprimed dendritic cells(DCs)is in clinical trials.Investigators are using patients’own immune systems to activate T-cells against recurrent or metastatic tumors.Following vaccination of DCs or attenuated tumor cells,clinical as well as radiological improvements have been noted due to migration and accumulation of cytotoxic T-cells(CTLs).CTLs mediated tumor cell killing resulted in extended survival in clinical trails and in preclinical models.Besides administration of primed DCs or attenuated or killed tumors cells to initiate the generation of CTLs,investigators have started making genetically altered T-cells(CTLs)to target specific tumors and showed in vivo migration and accumulation in the implanted or recurrent tumors using different imaging modalities.Our groups have also showed the utilization of both in vivo and in vitro techniques to make CTLs against glioma and used them as imaging probes to determine the sites of tumors.In this short review,the current status of vaccination therapy against glioma and utilization of CTLs as in vivo imaging probes to determine the sites of tumors and differentiate recurrent glioma from radiation necrosis will be discussed.

Effects of the Cytotoxic T-Cells on the Dynamics of Co-Infection of HIV-1 and Mycobacterium tuberculosis

Enhancement of the Human Immunodeficiency Virus (HIV) specific cytotoxic T-cells mechanisms in an HIV-1 and Mycobacterium tuberculosis (Mtb) co-infected individual seems to improve the clinical picture of an individual by reducing Acquired Immuno Deficiency Syndrome (AIDS) state progression rate. In this paper, we develop a system of deterministic differential equations representing the immune cells involved in an HIV-1 and Mtb co-infected individual. Results show that although the non-lytic arm of the HIV-1 cytotoxic T-cells affects the co-infection dynamics more than the lytic factors, a combination of both factors results in a more positive reduced progression to the AIDS state. This is due to the increased protection of the CD4+ T-cells by the CTL mechanisms by further reducing infections and replications by the HIV. Thus, HIV-1 specific CTLs mechanisms’ involvement is here recommended to be part of a solution to the HIV and Mtb co-infection problems.

Efficient Numerical Scheme for the Solution of HIV Infection CD4^(+)T-Cells Using Haar Wavelet Technique

In this paper,Haar collocation algorithmis developed for the solution of first-order ofHIV infection CD4^(+)T-Cells model.In this technique,the derivative in the nonlinear model is approximated by utilizing Haar functions.The value of the unknown function is obtained by the process of integration.Error estimation is also discussed,which aims to reduce the error of numerical solutions.The numerical results show that the method is simply applicable.The results are compared with Runge-Kutta technique,Bessel collocation technique,LADM-Pade and Galerkin technique available in the literature.The results show that the Haar technique is easy,precise and effective.

Machine learning-enhanced Monte Carlo and subset simulations for advanced risk assessment in transportation infrastructure

The maintenance of safety and dependability in rail and road embankments is of utmost importance in order to facilitate the smooth operation of transportation networks.This study introduces a comprehensive methodology for soil slope stability evaluation,employing Monte Carlo Simulation(MCS)and Subset Simulation(SS)with the"UPSS 3.0 Add-in"in MS-Excel.Focused on an 11.693-meter embankment with a soil slope(inclination ratio of 2H:1V),the investigation considers earthquake coefficients(kh)and pore water pressure ratios(ru)following Indian zoning requirements.The chance of slope failure showed a considerable increase as the Coefficient of Variation(COV),seismic coefficients(kh),and pore water pressure ratios(ru)experienced an escalation.The SS approach showed exceptional efficacy in calculating odds of failure that are notably low.Within computational modeling,the study optimized the worst-case scenario using ANFIS-GA,ANFIS-GWO,ANFIS-PSO,and ANFIS-BBO models.The ANFIS-PSO model exhibits exceptional accuracy(training R2=0.9011,RMSE=0.0549;testing R2=0.8968,RMSE=0.0615),emerging as the most promising.This study highlights the significance of conducting thorough risk assessments and offers practical insights into evaluating and improving the stability of soil slopes in transportation infrastructure.These findings contribute to the enhancement of safety and reliability in real-world situations.

Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma:A case report

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a non-Hodgkin lymphoma that originates in the central nervous system(CNS)and is exclusively limited to the CNS.Although most PCNSLs are diffuse large B-cell lymphomas,primary CNS T-cell lymphomas(PCNSTLs)are rare.PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging(MRI).To the best of our knowledge,non-enhancing PCNSTL has not been reported previously.CASE SUMMARY A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks.Initial MRI showed asymmetric T2-hyperintense lesions within the brain.No enhancement was observed on the contrast-enhanced T1 image.The initial diagnosis was neuro-Behçet’s disease.Despite high-dose steroid therapy,no alterations in the lesions were identified on initial MRI.The patient’s symptoms deteriorated further.An MRI performed one month after the initial scan revealed an increased lesion extent.Subsequently,brain biopsy confirmed the diagnosis of PCNSTL.The patient underwent definitive combined chemoradiotherapy.However,the patient developed bacteremia and died of septic shock approximately three months after diagnosis.CONCLUSION The absence of enhancement in the lesion did not rule out PCNSTL.A biopsy approach is advisable for pathological confirmation.

Mutations in Ras homolog family member A in patients with peripheral T-cell lymphoma and implications for personalized medicine

Genome sequencing has revealed frequent mutations in Ras homolog family member A(RHOA)among various cancers with unique aberrant profiles and pathogenic effects,especially in peripheral T-cell lymphoma(PTCL).The discrete positional distribution and types of RHOA amino acid substitutions vary according to the tumor type,thereby leading to different functional and biological properties,which provide new insight into the molecular pathogenesis and potential targeted therapies for various tumors.However,the similarities and discrepancies in characteristics of RHOA mutations among various histologic subtypes of PTCL have not been fully elucidated.Herein we highlight the inconsistencies and complexities of the type and location of RHOA mutations and demonstrate the contribution of RHOA variants to the pathogenesis of PTCL by combining epigenetic abnormalities and activating multiple downstream pathways.The promising potential of targeting RHOA as a therapeutic modality is also outlined.This review provides new insight in the field of personalized medicine to improve the clinical outcomes for patients.

Comparison of Block Design Nonparametric Subset Selection Rules Based on Alternative Scoring Rules

This article compares the size of selected subsets using nonparametric subset selection rules with two different scoring rules for the observations. The scoring rules are based on the expected values of order statistics of the uniform distribution (yielding rank values) and of the normal distribution (yielding normal score values). The comparison is made using state motor vehicle traffic fatality rates, published in a 2016 article, with fifty-one states (including DC as a state) and over a nineteen-year period (1994 through 2012). The earlier study considered four block design selection rules—two for choosing a subset to contain the “best” population (i.e., state with lowest mean fatality rate) and two for the “worst” population (i.e., highest mean rate) with a probability of correct selection chosen to be 0.90. Two selection rules based on normal scores resulted in selected subset sizes substantially smaller than corresponding rules based on ranks (7 vs. 16 and 3 vs. 12). For two other selection rules, the subsets chosen were very close in size (within one). A comparison is also made using state homicide rates, published in a 2022 article, with fifty states and covering eight years. The results are qualitatively the same as those obtained with the motor vehicle traffic fatality rates.

Plasmacytosis mimicking multiple myeloma in angioimmunoblastic T-cell lymphoma:A case report and review of literature

BACKGROUND Angioimmunoblastic T-cell lymphoma(AITL)is a common subtype of peripheral T-cell lymphoma.Approximately half of patients with AITL may concurrently present with hypergammaglobulinemia.Increased numbers of plasma cells in the bone marrow are commonly observed at diagnosis.These tumors mimic plasma cell myelomas,hindering a conundrum of clinical diagnoses and potentially delaying appropriate treatment.CASE SUMMARY A 78-year-old woman experienced poor appetite,weight loss of 5 kg,fatigue 2 months before presentation,and shortness of breath 2 d before presentation,but no fever or night sweats.Physical examination revealed splenomegaly and many palpable masses over the bilateral axillary regions,approximately>2 cm in size,with rubbery consistency and no tenderness.Blood tests revealed anemia and thrombocytopenia,lactate dehydrogenase level of 153 U/L,total protein level of 10.9 g/dL,albumin to globulin ratio of 0.2,and immunoglobulin G level more than the upper limit of 3000 mg/dL.The free kappa and lambda light chain concentrations were 451 and 614 mg/L,respectively.A pathological examination confirmed the diagnosis of AITL.The initial treatment was the cyclophosphamide,epirubicin,vincristine,and prednisolone regimen.Following this treatment,pleural effusion was controlled,and the patient was discharged in a stable condition and followed up in our outpatient department.CONCLUSION This report highlights the importance of differentiating reactive plasmacytosis from plasma cell myeloma in patients with hypergammaglobulinemia.A precise diagnosis of AITL requires a comprehensive evaluation,involving clinical,immunophenotypic,and histological findings conducted by a multidisciplinary team to ensure appropriate treatment.

Rare primary gastric peripheral T-cell lymphoma not otherwise specified:A case report

BACKGROUND Gastrointestinal lymphoma typically arises in the stomach,small bowel,or colorectum and is usually a B-cell lymphoma.However,primary T-cell lymp-homas originating in the stomach are particularly rare.Gastric peripheral T-cell lymphoma-not otherwise specified(PTCL-NOS)is an extremely rare subtype.CASE SUMMARY We report a 63-year-old male presenting with epigastric pain.Esophagogastro-duodenoscopy revealed a large ulcerative lesion in the gastric cardia.Biopsy and immunohistochemical profiling confirmed PTCL-NOS.Imaging indicated stage II disease involving the stomach and intra-abdominal lymph nodes.The patient is planned to undergo cyclophosphamide,doxorubicin,vincristine,and prednisone or cyclophosphamide,doxorubicin,vincristine,prednisone,and etoposide chemo-therapy.CONCLUSION This case highlights the necessity of considering PTCL-NOS in differential diag-noses of gastric lesions.Comprehensive histopathological and immunohistoche-mical analysis is crucial for accurate diagnosis and guiding treatment.

Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report

BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.

Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

BACKGROUND Advanced gastric cancer(AGC)remains a challenging malignancy with poor prognosis.The combination of oxaliplatin and trastuzumab has shown promising results in AGC treatment.This study aimed to investigate the effects of oxaliplatin and trastuzumab combination therapy on serum tumor markers and T lymphocyte subsets in patients with AGC and to explore their potential as predictive biomarkers for treatment response.AIM To investigate the impact of oxaliplatin and trastuzumab combination therapy on serum markers and T cell subsets in patients with AGC.METHODS This prospective study enrolled 60 patients with AGC.All patients received oxaliplatin(130 mg/m^(2),every 3 weeks)and trastuzumab(8 mg/kg loading dose,followed by 6 mg/kg every 3 weeks)for six cycles.Serum carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9),and cancer antigen 72-4(CA72-4)were measured before and after treatment.T-lymphocyte subsets,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were also evaluated.The clinical response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1.RESULTS After six cycles of treatment,the CEA,CA19-9,and CA72-4 serum levels significantly decreased compared to baseline levels(P<0.001).The percentages of CD3+and CD4+T lymphocytes increased significantly(P<0.05),whereas the percentage of CD8+T lymphocytes decreased(P<0.05).The CD4+/CD8+ratio also significantly increased after treatment(P<0.05).Patients with a higher decrease in serum tumor markers(≥50%reduction)and a higher increase in CD4+/CD8+ratio(≥1.5-fold)showed better clinical response rates(P<0.05).CONCLUSION Oxaliplatin and trastuzumab combination therapy effectively reduced serum tumor marker levels and modulated T lymphocyte subsets in patients with AGC.Combination therapy not only has a direct antitumor effect,but also enhances the immune response in patients with AGC.Serum tumor markers and T lymphocyte subsets may serve as potential predictive biomarkers for treatment response in patients with AGC receiving combination therapy.