Effect of Dietary Alanyl-glutamine Supplementation on Growth Performance, Development of Intestinal Tract, Antioxidant Status and Plasma Non-specific Immunity of Young Mirror Carp(Cyprinus carpio L.)

Exogenous alanyl-glutamine（Aln-Gln） was evaluated for its effects on growth performance, intestinal structure and function, antioxidant status and non-specific immunity of young carp（Cyprinus carpio L.）. Six diets supplemented with 0, 2.5, 5.0, 7.5, 10.0, or 15.0 g · kg-1 of Aln-Gln were fed to fish for 12 weeks. Supplementation with 7.5, 10.0, or 15.0 g · kg-1 of Aln-Gln significantly increased weight gain rate（WGR）, protein efficiency ratio（PER）, but feed conservation rate（FCR） and survival were not affected（P〉0.05）. The intestinal fold height and number, digestive enzyme, Na＋, K＋-ATPase activities was found to be significantly high（P〈0.05） with increasing dietary Aln-Gln supplementation up to 7.5 g · kg-1, but there were no significant differences for Aln-Gln supplementation from 7.5 to 15.0 g · kg-1. The glutathione peroxidase（GPX） activity, glutathione（GSH）, superoxide dismutase（SOD） activity increased and malondialdehyde（MDA） levels decreased significantly（P〈0.05） in the intestine, hepatopancreas, plasma and muscles. The plasma complement-3（C3） and complement-4（C4） levels were significantly（P〈0.05） improved at 5.0 g · kg-1 level and decreased when over 7.5 g · kg-1. The plasma lysozyme（LSZ） activity increased significantly（P〈0.05） at 7.5, 10.0, or 15.0 g · kg-1 level. In summary, the results showed that Aln-Gln improved growth performance, development and function of the intestine, the activity of the antioxidant defense system and the plasma non-specific immunity of the carps. The optimal Aln-Gln level was 8.24 g · kg-1 diet for WGR based on broken-line regression model analysis.

Effects of Size Grading on Growth and Non-Specific Immunity Factors of the Shrimp Litopenaeus vannamei Boone

The study aims to determine the effects of graded farming on growth performance and non-specific immunity factors of shrimp Litopenaeus vannamei Boone. Three size groups of shrimp, i.e., the small size group [Gs, with an average body length （BL） of （3.04 ± 0.36） cm and body weight （BW） （0.412± 0.35） g], the large group [GL, with a BL of （4.29±0.55） cm and BW of （1.098 ±0.42） g], and the ungraded group [Gm, with a BL of （3.47±0.81） cm and BW of （0.611 ±0.79） g], were reared under the same conditions for 8 wk. Growth performance and non- specific immunity factors were measured. The results showed that BW gain, biomass gain and the specific growth rate of body length （SGRL） were significantly influenced by size grading （one-way ANOVA, P 〈 0.05）. The peroxidase （POD） and antibacterial （Ua） activities of GL were lower than those of G. Superoxide dismutase （SOD） and lysozyme （U1） activities of Gm were lower than those of G. No significant difference （P = 0.121 〉 0.05） was found on phenoloxidase （PO） activity among the three size groups. Synthetically, size grading could enhance growth and rearing efficiency, and did not have a significant influence on the immunity of L. vannamei Boone. Therefore, graded fanning in L. vannamei Boone was feasible in the culture practice.

Effects of the Chinese Medicinal Herb Com plex Additives on Non-specific Immunity of Amursturgeon( Acipenser schrencki Brandt)

This study was to investigate the effects of aqueous decotion from three Chinese medicinal herb additives （ Cyrtomium fortunei, prescription I and prescription II） on non-specific immunity of 1 ＋ age old Amur sturgeon （Acipenser schrencki Brandt） by oral perfusion. Cyrtomiumfortunei, prescription I and prescription II were orally given to 15 fishes for each experimental group once a day, with the concentration of 9,175 and 36 g/S0 kg body weight, respectively. The administration was lasted for 14 days. Meanwhile, distilled water was orally given as the control. After the experiment, some of the experimental fishes were stimulated with high temperature （30 ℃ ） for two hours. Sampling was performed from fishes treated at 22 ℃ and 30 ℃ for measuring the protein content in the serum, phagocytic activity of leucocytes and the activity of the lysozyme in six tissues. The results indicated that Cyrtomiumfortunei and prescription II could help to enhance the content of various proteins and the phagocytic activity of leucocytes. There was no significant change in the effects between these two additives at either the normal temperature or high temperature. Prescription I did not show an obvious effect on the immunity of fishes at the normal temperature, but it did in promo- ting high-efficiency response and improving immunoregulation of fish shocked by some stimuli.

Effect of Ammonia-Nitrogen Stress on Non-specific Immunity of Hybrid Tilapia(Oreochromis niloticus× Oreochromis areus)

The juveniles of hybrid tilapia （ Oreochromis niloticus x Oreochromis areus） were exposed to ananonia-nitrogen （N） （0, 2.5, 5, 10 and 20 mg/L） for 0, 12, 24, 48 and 72 h to evaluate the effect of ammonia-N stress on their non-specific immunity. Results show that the activity of serum lysozyme decreased signifi- candy with extension of stress time （P 〈 0.05）. The total antioxidant capacity （T-AOC） and activity of antioxidase in liver were significantly affected. The activi- ty of T-AOC and total superoxide dismutase （T-SOD） of fish exposed to ammonia-N were initially decreasing then increasing （ P 〈 0.05 ）. Activities of catalase （CAT） and glutathione peroxidase （GSH-Px） were correlated with concentrations of ammonia-N. Fish exposed to lower concentrations （2.5 mg/L or 5 mg/L） showed decreased CAT activity within 24 h （P 〈 0.05 ）, while those exposed to higher concentrations （10 mg/L or 20 mg/L） initially showed increased then decreased activity of CAT. Except for the highest concentration groups, fish exposed to ammonia-N showed inductive activity of GSH-Px （ P 〈 0.05 ）. Under the ex- perimental conditions, non-specific immunity of tilapia was affected by ammonia-N stress, and the impact was increased with increased concentration and extension of time.

Influences of immersion bathing in Bacillus velezensis DY-6 on growth performance,non-specific immune enzyme activities and gut microbiota of Apostichopus japonicus

In this study, the influences of immersion bathing in different concentrations of Bacillus velezensis DY-6 on the body weight gain rate and non-specific immune enzyme activities of the coelom fluid of sea cucumber (Apostichopus japonicus) were determined in order to obtain the optimum bacterial concentration. The gut microbiota change in A. japonicus was then analyzed through high-throughput sequencing during the immersion bathing in B. velezensis DY-6 at the optimum concentration for 49 d. The results illustrate that the body weight growth rate of all bathing groups was higher than that of the control. The highest growth rate (25.3%) was achieved when the bacterial concentration was 1×10^3 CFU/mL. The activities of non-specific immune enzymes (ACP, AKP, SOD and LZM) of all bathing groups increased, and the activities of the enzymes of groups bathed with the bacterium at 1×10^3 and 1×10^4 CFU/mL reached the highest on day 21 and day 28. Taking the growth rate and economic cost into consideration, the optimum concentration of B. velezensis DY-6 was 1×10^3 CFU/mL. The influences of immersion bathing in B. velezensis DY-6 at 1×10^3 CFU/mL on the gut microbiota of A. japonicus were then evaluated through 16S rDNA sequencing analysis. Results showed that the gut microbiota changed with the addition of B. velezensis DY-6, and the richness and diversity of the gut microbiota peaked twice on day 14 and day 21, respectively. In association with the non-specific immune enzyme activities and if day 28 was selected as the dividing point, the community structure of the gut microbiota could be obviously divided into two types. The correlation analysis revealed that the non-specific immune enzyme activities were correlated significantly to some gut bacteria (in the phyla Firmicutes, Proteobacteria, and Bacteroidetes) after immersion bathing in B. velezensis DY-6. Our findings will provide the theoretical foundation for probiotic application in sea cucumber farming.

Pivotal role of long non-coding ribonucleic acid-X-inactive specific transcript in regulating immune checkpoint programmed death ligand 1 through a shared pathway between miR-194-5p and miR-155-5p in hepatocellular carcinoma

BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.

PTPN22 and islet-specific autoimmunity:What have the mouse models taught us?

An allelic variant of the protein tyrosin phosphatase non-receptor 22(PTPN22) gene, PTPN22 R620 W, constitutes the strongest non-HLA genetic risk factor for the development of type 1 diabetes(T1D). A numberstudies using mouse models have addressed how PTPN22 predisposes to T1D. PTPN22 downmodulation, overexpression or expression of the variant gene in genetically manipulated mice has generated controversial results. These discrepancies probably derive from the fact that PTPN22 has differential effects on innate and adaptive immune responses. Moreover, the effects of PTPN22 are dependent on other genetic variables. Here we discuss these findings and try to explain the discrepancies. Exploring the mechanism by which PTPN22 contributes to islet-specific autoimmunity could help us understand its role in T1D pathogenesis and exploit it as a potential therapeutic target to prevent the disease.

Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases

BACKGROUND： There is a growing evidence that matrix metalloproteinase （MMP）-2 and MMP-9 （gelatinases） play an important role in the pathogenesis of numerous disorders, especially with inflammatory etiology and extracellular matrix （ECM） remodeling. Despite the fact that gelatinases involve in liver cirrhosis is provided in the literature, their role in the pathogenesis of chronic pancreatitis and non-specific inflammatory bowel diseases is still under investigation. DATA SOURCES： We carried out a PubMed search of Englishlanguage articles relevant to the involvement of gelatinases in the pathogenesis of liver fibrosis, pancreatitis, and non-specific inflammatory bowel diseases. RESULTS： The decreased activity of gelatinases, especially MMP-2, is related to the development of liver fibrosis, probably due to the decrease of capability for ECM remodeling. Similar situation can be found in chronic pancreatitis; however, reports on this matter are rare. The presence of non-specific inflammatory bowel diseases results in MMP-9 activity elevation. CONCLUSION： The fluctuation of gelatinases activity during liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases is observed, but the exact role of these enzymes demands further studies.

The Introduction of Specific Water and Maximum Airborne Specific Water &the Improvement of Dynamic Equations on Non-Uniform Saturated Moist Atmosphere

To eliminate the irrational supposition that condensed liquid water always falls immediately, specific water m?and maximum airborne specific water mm are introduced into the dynamic framework on non-uniform saturated moist atmosphere (m?is the ratio of the airborne liquid water mass to the moist air mass in unit cubage moist air, mm is its maximum value with , , and are airborne coefficient, vertical velocity and saturated specific humidity respectively). The balance equation between water vapor and airborne liquid water is derived. From the balance equation, a new formula of precipitate rate is got. The analysis shows that in the air stream with some upward vertical velocity ( ), the condensed liquid water can precipitate under the condition with (q is specific humidity) and? only, otherwise it is detained in the air and becomes airborne liquid water. Not only does precipitating liquid water contain condensed liquid water, but also contains converged and existing airborne liquid water. Following above discussion, improved dynamic equations on non-uniform saturated moist atmosphere are provided.

Preclinical Verification of Modulated Electro-Hyperthermia—Part III. Immunogenic Effects

The modulated electro-hyperthermia (mEHT) method is a unique approach that utilizes all the essential apoptotic pathways through an external radiofrequency (RF) signal. The high-frequency RF is amplitude-modulated and coupled capacitively to the target. The provided energy triggers the death receptors and FAS-FADD complexes in the malignant cells. Multi-pathway apoptosis produces immunogenic cell death (ICD). This ICD provides intracellular information about cancer cells by releasing damage-associated molecular patterns (DAMP), including membrane expression of calreticulin (CRT) and extracellular ATP, HMGB1, and HSP70, executing tumor-specific antigen presentation. The antigen-presenting cells (APCs) play a crucial role in reestablishing immune surveillance and hampering the tumor cells’ ability to hide, thereby evading immune attacks. The matured DCs (generally APCs) produce tumor-specific killer and helper T-cells, which have the potential to be active in distant metastases from the treated location. This unique mechanism of action underscores its potential in cancer treatment and extends the local mEHT treatment to the whole body anticancer therapy with an abscopal effect.

Specific heat of the non-centrosymmetric superconductor Re_3 W

The alloys of non-centrosymmetric superconductor, Re3W, which were reported to have an ^-Mn structure [P. Greenfield and P. A. Beck, J. Metals, N. Y. 8, 265 （1959）] with Tc = 9K, are prepared by arc melting. The values of ac susceptibility and the low-temperature specific heat of these alloys are measured. It is found that there are two superconducting phases coexisting in the samples with Tc1 ≈ 9 K and Tc2 ≈ 7K, which are both non-centrosymmetric in structure as reported previously. By analysing the specific heat data measured in various magnetic fields down to a temperature of 1.8 K, we find that the absence of the inversion symmetry does not lead to an obvious deviation from an s-wave pairing symmetry in Re3W.

Research Progress of Systemic Immune Inflammatory Index in Prostate Cancer

Prostate cancer has gradually risen to become the second most common cancer threatening men’s health, and prostate-specific antigen (PSA), as the main screening indicator for prostate cancer, has the defects of low specificity and insufficient diagnostic efficacy. As a novel inflammatory index based on neutrophil, lymphocyte and platelet counts, the systemic immune-inflammation index (SII) has recently become a more powerful biomarker for predicting the occurrence and progression of various malignancies. SII reflects the systemic inflammatory response of prostate cancer patients in a more balanced manner, and has higher predictive value than neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). High SII values are often associated with cancer progression and poor prognosis. This article reviews the research progress of SII in prostate cancer, in order to provide guidance for clinical practice.

Task-Specific Gait Analysis: Faller versus Non-Faller Comparative Study

In this paper, a comparative analysis of walking patterns during different cognitive states is conducted, followed by the classification of our database into Fallers and Non-fallers;by Fallers we describe subjects with repeated falling history. Vertical Ground Reaction Forces (VGRF) acquired from underneath the heel and toes of both feet are processed and analyzed for that endeavor. The subjects underwent three levels of tasks: 1) Single task: Walking at self-selected-speed (MS), 2) Dual task: Walking while performing a verbal fluency task (MF) and 3) Complex Dual task: Walking while counting backwards (MD).The ultimate objective of our research is fall prediction among the elderly by characterizing the variation of time-domain feature of Gait signals. For that, walking VGRF is analyzed and tested for the existence of indicators of the effect of dual task on subject falling susceptibility, whether parametric or pattern-wise analysis. As a result to our work, dual task in Fallers VGRF signals were recognized at 74% while at those non-fallers were recognized at 85%. Most importantly, subjects with history of fall have shown more potential to change the way they walk while performing mathematical cognitive task.

Thermal Therapy in Patients Suffering from Non-Specific Chronic Low Back Pain—A Systematic Review

Thermal therapy is frequently used as an adjunct to treatment in patients suffering from chronic low back pain. It is also an inherent part of patients’ self-administered pain treatment. This review aims to update the evidence for thermal therapy treatments in non-specific chronic low back pain patients and to rate the methodological quality of the corresponding clinical trials. Previous studies have reported contradictory evidence for the effectiveness of thermal therapy. An electronic search on MEDLINE (PubMed), PEDro, CENTRAL and CINHAL databases was conducted between May 2016 and February 2018. Clinical trials comparing local thermal therapy to conservative or no treatment were assessed for eligibility. Pain, physical function and global health were defined as outcome parameters. A total of n = 9 studies met the inclusion criteria. All of them applied an electrophysical agent as the thermal treatment: continuous ultrasound (n = 6), short-wave diathermy (n = 2), microwave diathermy (n = 1). Out of the n = 6 studies on ultrasound treatment, n = 2 reported significant within and between-group results for pain reduction after 4 to 6 weeks of treatment. Both short-wave diathermy studies demonstrated significant between-group results for pain reduction after 3 weeks of treatment. Contradictory results for all other observed outcome parameters were reported regardless of the intervention. Moreover, significant within-group results for the control groups questioned the effectiveness of the intervention treatments. Therefore, the effect of thermal therapy, (electrophysical agents), is not superior to any control treatment except for ultrasound treatment on short-term pain reduction.

Cross talk of the immune system in the adipose tissue and the liver in non-alcoholic steatohepatitis: Pathology and beyond

Non-alcoholic steatohepatitis(NASH) is considered to be the hepatic manifestation of the metabolic syndrome, thus has a tight correlation with systemic metabolic impairment. The complex mechanisms underlying the pathogenesis of NASH involve different organs and systems that cross talk together contributing to the onset of NASH. A crucial role is played by inflammatory mediators, especially those deriving from the adipose tissue and the liver, which are involved in the cascade of inflammation, fibrosis and eventually tumorigenesis. In this setting cytokines and adipokines as well as immunity are emerging drivers of the key features of NASH. The immune system participates in this process with disturbances of the cells constituting both the innate and the adaptive immune systems that have been reported in different organs, such as in the liver and in the adipose tissue, in clinical and preclinical studies. The role of the immune system in NASH is increasingly studied, not only because of its contribution to the pathogenetic mechanisms of NASH but also because of the new potential therapeutic options it offers in this setting. Indeed, novel treatments acting on the immune system could offer new options in the management of NASH and the correlated clinical consequences.

防风多糖体内外免疫调节活性研究

目的采用体内外多指标免疫调节活性评价方法,研究防风多糖体内外免疫功能的调节作用。方法体外实验选用RAW 264.7小鼠巨噬细胞系,采用CCK-8法检测巨噬细胞的增殖能力,中性红染色法检测巨噬细胞的吞噬能力,Griess法测定巨噬细胞NO释放量,酶联免疫吸附法(ELISA)测定巨噬细胞肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)释放量。体内实验选用环磷酰胺诱导的免疫低下BALB/c小鼠,通过碳粒廓清实验探讨防风多糖对小鼠网状内皮系统吞噬功能,以小鼠免疫器官指数评价防风多糖对小鼠免疫器官的影响,并采用ELISA法测定小鼠体内免疫球蛋白(IgM、IgG、IgA)和补体(C3、C4)含量。结果体外实验结果表明,防风多糖能够显著提高巨噬细胞的增殖和吞噬能力,并促进巨噬细胞释放NO、TNF-α和IL-6,但对IL-1β的释放量影响不显著。体内实验结果表明,防风多糖可使免疫低下小鼠模型的吞噬能力和免疫器官指数显著提高,并使免疫低下小鼠体内的免疫球蛋白(IgM、IgG、IgA)和补体(C3、C4)的含量升高。结论防风多糖在体内外水平均具有较好的免疫调节活性,参与调节机体的特异性免疫和非特异性免疫。

Study on the Changes of Immune Factors in Different Stages of Non-Small Cell Lung Cancer Chemotherapy

Objective: To analyze various immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) and peripheral blood of patients with non-small cell lung cancer (NSCLC) at different times after chemotherapy. Changes in CD4+, CD8+, Th17 and IgG, IgM, and IgA levels. Methods: A total of 118 NSCLC patients who attended the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to September 2021 were selected as the research objects, and the patients were analyzed at different time points (before chemotherapy, after the first chemotherapy, and after the second chemotherapy). The effects of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r, CD4+, CD8+ Th17, IgG, IgM and IgA levels in peripheral blood at different time points (before chemotherapy, after the first chemotherapy and after the second chemotherapy) were analyzed. The changes of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r and the levels of CD4+, CD8+ Th17, IgG, IgM and IgA in peripheral blood were compared at each time point. Results: NKG2D, IL-12, IL-15, IL-18, TNF-a, IFN-r gradually decreased before chemotherapy, one week after chemotherapy, and two weeks after chemotherapy, the difference was statistically significant, but DC cells were not significant Variety. CD4+ and CD8+ both increased significantly, and the levels of Th17, IgG, IgM, and IgA gradually decreased. Conclusion: In the course of chemotherapy, all immune factors except DC cells were significantly decreased compared with those before chemotherapy, and the decrease of immune factors except DC cells was positively correlated with the length of chemotherapy cycle. If additional immunotherapy is needed, it should be carried out in the early stage of chemotherapy.

Effect of Chemotherapy on Immune Factors in Patients with Non-Small Cell Lung Cancer

Objective: To analyze the effects of different stages of chemotherapy on the immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) in patients with non-small cell lung cancer (NSCLC). Methods: 106 patients who met the research requirements in the Department of oncology of the Affiliated Hospital of Chengde Medical College from September 2018 to June 2021 were included in the study. The blood levels of interleukin-12 (IL-12), interleukin-15 (IL-15), interleukin-18 (IL-18), dendritic cells (DC cells), tumor necrosis factor A (TNF-a) and the levels of immune interferon (IFN-r) and NK cell activating receptor (NKG2D) in blood before chemotherapy, after the first chemotherapy and after the second chemotherapy were analyzed. Results: Except for the viability of DC cells and DC cells, all other immune factor groups showed statistical differences. Conclusion: Chemotherapy will have a negative effect on all immune factors except DC cells. The effect of immune factors will be weakened according to the increase of the chemotherapy cycle. Therefore, immunotherapy for non-small cell lung cancer needs to be carried out before chemotherapy or in the early stage of chemotherapy to achieve better results.

Effects of Chemotherapy on Peripheral Blood NK Cell Receptor NKG2D and Related Immune Cytokines in Patients with Non-Small Cell Lung Cancer

Objective: To analyze the effect of chemotherapy on peripheral blood NK cell receptor NKG2D and related immune cytokines (IL-12, IL-15, IL-18) in patients with non-small cell lung cancer (NSCLC). Methods: A total of 48 patients with NSCLC who visited the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to September 2019 were selected as the study subjects. Changes in the expression levels of NKG2D, IL-12, IL-15 and IL-18 in peripheral blood of patients at different time points (before chemotherapy, after the first chemotherapy and after the second chemotherapy) were analyzed to investigate the correlation between NKG2D and IL-12, IL-15 and IL-18 in peripheral blood at each time point. Results: The expression levels of NKG2D, IL-15, and IL-18 in the peripheral blood of the patient before chemotherapy, after the first chemotherapy, and after the second chemotherapy gradually decreased. After the first chemotherapy and the second chemotherapy, the peripheral blood IL-12 was significantly lower than before chemotherapy, and IL-12 in peripheral blood after the second chemotherapy was slightly increased compared with that after the first chemotherapy. The comparison of each factor at different time points was statistically significant (all P<span style="font-family: ">0.05). Pearson correlation analysis showed that after the first chemotherapy, NKG2D in peripheral blood was positively correlated with IL-18 (r = 0.342, P = 0.031);after the second chemotherapy, NKG2D in peripheral blood was positively correlated with IL-18 (r = 0.411, P = 0.023), negatively correlated with IL-15 (r = -0.451, P = 0.001). Conclusion: There was no significant change in the number of NK cells in the peripheral blood of NSCLC patients after chemotherapy, while NKG2D and related immune cytokines decreased, which may be one of the mechanisms for the suppression of immune function in patients, and this provides a potential target for immunotherapy in patients.

Immunotherapy in Early Stage Non-Small Cell Lung Cancer

Immune-checkpoint inhibitors are extensively used in cancer treatment and have transformed the therapeutic landscape by inducing durable responses. Immunotherapy with checkpoint inhibitors targeting programmed death 1 (PD-1) receptor and programmed death ligand-1 (PDL-1) are used alone or with chemotherapy for treatment of metastatic non-small cell lung cancer (NSCLC). There is a great need for improving outcomes of patients with early stage NSCLC after surgical resection and with recent F. D. A. approval, immune checkpoint inhibitors are used as neoadjuvant or adjuvant therapy to enable curative resection and prevent or delay disease progression. In this article, we review the clinical studies evaluating the role of adjuvant and neoadjuvant immune checkpoint inhibitors in NSCLC and discuss the role of immunotherapy with radiation therapy in locally advanced non-metastatic NSCLC.