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Background: Tumor immunotherapy can not only eliminate the primary lesion, but also produce long-term immune memory, effectively inhibiting tumor metastasis and recurrence. However, immunotherapy also showed plenty of limitations in clinical practice. In recent years, the combination of nanomaterials and immunotherapy has brought new light for completely eliminating tumors with its fabulous anti-tumor effects and negligible side effects. Methods: The Core Collection of Web of Science (WOSCC) was used to retrieve and obtain relevant literatures on antitumor nano-immunotherapy since the establishment of the WOSCC. Bibliometrix, VOSviewer, CiteSpace, GraphPad Prism, and Excel were adopted to perform statistical analysis and visualization. The annual output, active institutions, core journals, main authors, keywords, major countries, key documents, and impact factor of the included journals were evaluated. Results: A total of 443 related studies were enrolled from 2004 to 2022, and the annual growth rate of articles reached an astonishing 16.85%. The leading countries in terms of number of publications were China and the United States. Journal of Controlled Release, Biomaterials, Acta Biomaterialia, Theranostics, Advanced Materials, and ACS Nano were core journals publishing high-quality literature on the latest advances in the field. Articles focused on dendritic cells and drug delivery accounted for a large percentage in this field. Key words such as regulatory T cells, tumor microenvironment, immune checkpoint blockade, drug delivery, photodynamic therapy, photothermal therapy, tumor-associated macrophages were among the hottest themes with high maturity. Dendritic cells, vaccine, and T cells tend to become the popular and emerging research topics in the future. Conclusions: The combined treatment of nanomaterials and antitumor immunotherapy, namely antitumor nano-immunotherapy has been paid increasing attention. Antitumor nano-immunotherapy is undergoing a transition from simple to complex, from phenotype to mechanism. [ABSTRACT FROM AUTHOR]

Background: High-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16. Methods: In this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively. Results: A total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes. Conclusion: The sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China. [ABSTRACT FROM AUTHOR]

Background: Among people living with HIV (PLHIV) on antiretroviral therapy (ART), the mortality of immunological non-responders (INRs) is higher than that of immunological responders (IRs). However, factors associated with immunological non-response following ART are not well documented. Methods: We obtained data for HIV patients from the National Free Antiretroviral Treatment Program database in China. Patients were grouped into IRs (CD4 cell count ≥ 350 cells/μl after 24 months' treatment), immunological incomplete responders (ICRs) (200–350 cells/μl) and INRs (< 200 cells/μl). Multivariable logistic regression was used to assess factors associated with immunological non-response. Results: A total of 3900 PLHIV were included, among whom 2309 (59.2%) were IRs, 1206 (30.9%) ICRs and 385 (9.9%) INRs. In multivariable analysis, immunological non-response was associated with being male (2.07, 1.39–3.09), older age [40–49 years (vs. 18–29 years): 2.05, 1.29–3.25; 50–59 years: 4.04, 2.33-7.00; ≥ 60 years: 5.51, 2.84–10.67], HBV co-infection (1.63, 1.14–2.34), HCV co-infection (2.01, 1.01–4.02), lower CD4 + T cell count [50–200 cells/μl (vs. 200–350 cells/μl): 40.20, 16.83–96.01; < 50 cells/μl: 215.67, 85.62-543.26] and lower CD4/CD8 ratio (2.93, 1.98–4.34) at baseline. Compared with patients treated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) based regimens, those receiving protease inhibitors (PIs) based regimens were less likely to be INRs (0.47, 0.26–0.82). Conclusions: We found a sizable immunological non-response rate among HIV-infected patients. Being male, older age, coinfection with HBV and HCV, lower CD4 + T cell count and lower CD4/CD8 ratio are risk factors of immunological non-response, whereas PIs-based regimens is a protective factor. [ABSTRACT FROM AUTHOR]

Background: Classical swine fever and porcine reproductive and respiratory syndrome have seriously affected the development of the swine breeding industry in China. Vaccine immunization remains the main way to prevent these infections. The aim of this study was to establish an optimized protocol for vaccine immunization against classical swine fever virus (CSFV) and porcine reproductive and respiratory syndrome virus (PRRSV). Methods: Blood samples were collected from the anterior vena cava of pigs after immunization, and blood indices, secreted levels of specific antibodies and neutralizing antibodies associated with humoral immunity, the proliferation capacity of T lymphocytes as a measure of cellular immunity, and secreted levels of IFN-γ and TNF-α were determined. Results: The results showed that simultaneous immunization against CSFV and PRRSV infections induced strong and specific humoral and T-cellular immune responses, high levels of cytokine IFN-γ secretion and delayed secretion of cytokine TNF-α. Moreover, significantly higher lymphocyte percentages and red blood cell and leukocyte counts were found in the group simultaneously immunized against CSFV and PRRSV. However, no statistically significant differences were observed in hemoglobin values, neutrophil counts, and median cell percentages among the S + PRRS, PRRS-S, and S-PRRS groups. Conclusion: This study demonstrated that simultaneous immunization against CSFV and PRRSV had the advantages of inducing a rapid, enhanced, and long-lasting immune response. These findings provide a theoretical basis for the establishment of a reasonable and optimized vaccine immunization protocol against CSFV and PRRSV in combination with a variety of other vaccine inoculations. [ABSTRACT FROM AUTHOR]

Background: Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps. Methods: A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry. Results: Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4+CD44highCD62L− T cells (effector memory T cells) and CD8+CD44highCD62L+ T cells (central memory T cells) in rPocDBP-RII‑immunized mice. Conclusions: PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4+ and CD8+ T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities. [ABSTRACT FROM AUTHOR]

Background: Anti-PD-1 antibodies have been approved for treating several cancer. However, data regarding the safety and efficacy of these agents in HIV-infected patients with cancer is lacking, because these patients are frequently omitted from clinical trials. Objectives: The primary aim of our research is to assess the safety, activity, and long-term outcomes of PD-1 inhibitors in the treatment of HIV-infected patients with advanced cancer. Method: We retrospectively analyzed data from HIV-infected patients with advanced cancers who were treated with PD-1 inhibitors at Shanghai Public Health Clinical Center, Shanghai, China. Results: Fifteen HIV-infected patients (all are men; asian; median age, 44) with cancer who were treated with chemotherapy and/or combined the other oncology treatments [along with combined antiretroviral therapy (cART)] prior to Sintilimab (12 out of 15) or Nivolumab (1 out of 11) or Camrelizumab (2 out of 11) injection were identified. Eight patients responded to treatment (disease control rate 53.3%), with 1 got partial response (PR) and 7 were stable. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 including anemia, leukopenia, hyperglycemia, granulocytopenia, and thrombocytopenia. Eight patients (53.3%) experienced treatment-related AEs (TRAEs) with grades 3/4including myelosuppression, infection, and neurological disorders. CD4+ T cell count and plasma HIV RNA remained stable throughout the treatment. Conclusions: When used in HIV-infected patients with advanced malignancies, PD-1 inhibitors tend to have favorable efficacy, manageable side effects, and no deteriorated impacts on plasma HIV-RNA and CD4+ T cell count. [ABSTRACT FROM AUTHOR]

Zeta(ζ)-Chain Associated Protein Kinase 70 kDa (ZAP-70) deficiency is a rare autosomal recessive primary immunodeficiency disease. Little is known about this disease. In this study, we report two patients to extend the range of clinical phenotypes and immunophenotypes associated with ZAP-70 mutations. We describe the clinical, genetic, and immunological phenotypes of two patients with ZAP-70 deficiency in China, and the data are also compared with the literature. Case 1 presented with leaky severe combined immunodeficiency with low to the absence of CD8 + T cells, while case 2 suffered from a recurrent respiratory infection and had a past medical history of non-EBV-associated Hodgkin's lymphoma. Sequencing revealed novel compound heterozygous mutations in ZAP-70 of these patients. Case 2 is the second ZAP-70 patient presenting a normal CD8 + T cell number. These two cases have been treated with hematopoietic stem cell transplantation. Selective CD8 + T cell loss is an essential feature of the immunophenotype of ZAP-70 deficiency patients, but there are exceptions. Hematopoietic stem cell transplantation can provide excellent long-term immune function and resolution of clinical problems. [ABSTRACT FROM AUTHOR]

Zeta(ζ)-Chain Associated Protein Kinase 70 kDa (ZAP-70) deficiency is a rare autosomal recessive primary immunodeficiency disease. Little is known about this disease. In this study, we report two patients to extend the range of clinical phenotypes and immunophenotypes associated with ZAP-70 mutations. We describe the clinical, genetic, and immunological phenotypes of two patients with ZAP-70 deficiency in China, and the data are also compared with the literature. Case 1 presented with leaky severe combined immunodeficiency with low to the absence of CD8 + T cells, while case 2 suffered from a recurrent respiratory infection and had a past medical history of non-EBV-associated Hodgkin's lymphoma. Sequencing revealed novel compound heterozygous mutations in ZAP-70 of these patients. Case 2 is the second ZAP-70 patient presenting a normal CD8 + T cell number. These two cases have been treated with hematopoietic stem cell transplantation. Selective CD8 + T cell loss is an essential feature of the immunophenotype of ZAP-70 deficiency patients, but there are exceptions. Hematopoietic stem cell transplantation can provide excellent long-term immune function and resolution of clinical problems. [ABSTRACT FROM AUTHOR]

Background: Classical swine fever and porcine reproductive and respiratory syndrome have seriously affected the development of the swine breeding industry in China. Vaccine immunization remains the main way to prevent these infections. The aim of this study was to establish an optimized protocol for vaccine immunization against classical swine fever virus (CSFV) and porcine reproductive and respiratory syndrome virus (PRRSV). Methods: Blood samples were collected from the anterior vena cava of pigs after immunization, and blood indices, secreted levels of specific antibodies and neutralizing antibodies associated with humoral immunity, the proliferation capacity of T lymphocytes as a measure of cellular immunity, and secreted levels of IFN-γ and TNF-α were determined. Results: The results showed that simultaneous immunization against CSFV and PRRSV infections induced strong and specific humoral and T-cellular immune responses, high levels of cytokine IFN-γ secretion and delayed secretion of cytokine TNF-α. Moreover, significantly higher lymphocyte percentages and red blood cell and leukocyte counts were found in the group simultaneously immunized against CSFV and PRRSV. However, no statistically significant differences were observed in hemoglobin values, neutrophil counts, and median cell percentages among the S + PRRS, PRRS-S, and S-PRRS groups. Conclusion: This study demonstrated that simultaneous immunization against CSFV and PRRSV had the advantages of inducing a rapid, enhanced, and long-lasting immune response. These findings provide a theoretical basis for the establishment of a reasonable and optimized vaccine immunization protocol against CSFV and PRRSV in combination with a variety of other vaccine inoculations. [ABSTRACT FROM AUTHOR]

Background: Classical swine fever and porcine reproductive and respiratory syndrome have seriously affected the development of the swine breeding industry in China. Vaccine immunization remains the main way to prevent these infections. The aim of this study was to establish an optimized protocol for vaccine immunization against classical swine fever virus (CSFV) and porcine reproductive and respiratory syndrome virus (PRRSV). Methods: Blood samples were collected from the anterior vena cava of pigs after immunization, and blood indices, secreted levels of specific antibodies and neutralizing antibodies associated with humoral immunity, the proliferation capacity of T lymphocytes as a measure of cellular immunity, and secreted levels of IFN-γ and TNF-α were determined. Results: The results showed that simultaneous immunization against CSFV and PRRSV infections induced strong and specific humoral and T-cellular immune responses, high levels of cytokine IFN-γ secretion and delayed secretion of cytokine TNF-α. Moreover, significantly higher lymphocyte percentages and red blood cell and leukocyte counts were found in the group simultaneously immunized against CSFV and PRRSV. However, no statistically significant differences were observed in hemoglobin values, neutrophil counts, and median cell percentages among the S + PRRS, PRRS-S, and S-PRRS groups. Conclusion: This study demonstrated that simultaneous immunization against CSFV and PRRSV had the advantages of inducing a rapid, enhanced, and long-lasting immune response. These findings provide a theoretical basis for the establishment of a reasonable and optimized vaccine immunization protocol against CSFV and PRRSV in combination with a variety of other vaccine inoculations. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the T-cell receptor (TCR) repertoire in patients with acute coronary syndrome (ACS).Methods: The TCR repertoires of 9 unstable angina patients (UA), 14 acute myocardial infarction patients (AMI) and 9 normal coronary artery (NCA) patients were profiled using high-throughput sequencing (HTS). The clonal diversity of the TCR repertoires in different groups was analyzed, as well as the frequencies of variable (V), diversity (D) and joining(J) gene segments.Results: ACS patients including UA and AMI, showed reduced TCRβ diversity than NCA patients. ACS patients presented higher levels of clonal expansion. The clonotype overlap of complementarity determining region 3(CDR3) was significantly varied between different groups. A total of 10 V genes and 1 J gene were differently utilized between ACS and NCA patients. We identified some shared CDR3 amino acid sequences that were presented in ACS but not in NCA patients.Conclusions: This study revealed the distinct TCR repertoires in patients with ACS and demonstrated the presence of disease associated T-cell clonotypes. These findings suggested a role of T cells in ACS and provided a new way to explore the mechanisms of ACS. [ABSTRACT FROM AUTHOR]

Background: Hantaan virus (HTNV) can cause hemorrhagic fever with renal syndrome (HFRS) in humans with severe morbidity and high mortality. Although inactivated HFRS vaccines are given annually for prevention in populations, China still has the highest number of HFRS cases and deaths worldwide. Consequently, vaccination for HFRS requires the development of novel, more effective vaccines. Epitope peptide vaccines have been developed rapidly in recent years and are considered a novel approach for the prevention of infection. Specifically, the multiple antigenic peptide (MAP) design with preferable immunogenicity can arouse a satisfactory immune response for vaccination. However, there are few reports on the design and evaluation of MAP for HTNV. Methods: Three HLA-A*02-restricted 9-mer cytotoxic T lymphocyte (CTL) epitopes on HTNV glycoprotein and one HLA-A*02-restricted 9-mer CTL epitope on the HTNV nucleocapsid, which have been proven to be immunoprotective in our previous study, were selected for the design of HTNV MAP. A four-branched HTNV MAP was evaluated by the IFN-γ-secreting enzyme-linked immunospot assay and proliferation induction capacity of CD8+ T cells and compared with the single HTNV CTL epitope in 17 HLA-A*02+ patients with HFRS. The Mann–Whitney U test was used for comparison of parameters between different subject groups. Results: The macromolecular HTNV MAP was designed with a polylysine core and four radially branched single CTL epitope chains. Importantly, HTNV MAP could stimulate CD8+ T cell secretion of IFN-γ in HLA-A*02+ patients with HFRS. The frequency of IFN-γ-secreting CD8+ T cells in the MAP stimulation group was significantly higher than that in the single HTNV CTL epitope stimulation groups (P < 0.005). Meanwhile, the activity of IFN-γ-secreting CD8+ T cells in the HTNV MAP group was also higher than that of the single CTL epitope groups (P < 0.05). Moreover, there was a much stronger ability of HTNV MAP to stimulate CD8+ T cell proliferation compared with that of a single HTNV CTL epitope. Conclusions: The designed HTNV MAP could induce CTL responses ex vivo and may be considered a candidate for the design and development of novel HTNV peptide vaccines. [ABSTRACT FROM AUTHOR]

Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay.Methods: ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2-3, ≤ 2 log10 copies/106 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log10 copies/106 PBMCs) at week 96 were evaluated using a logistic regression model.Results: Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log10 copies/106 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log10 copies/106 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4+ T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log10 copies/106 PBMCs.Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log10 copies/106 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART. [ABSTRACT FROM AUTHOR]

Background: Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of immune regulation, and HLH patients with mutations in genes including PRF1, UNC13D, STX11, STXBP2, SH2D1A, XIAP, and ITKwere reported to be primary HLH. Due to the different treatment options, the differentiation between primary and secondary HLH is critical. Our previous studies have showed that a Th1/Th2 cytokine profile is diagnostic for HLH, yet the cytokine profiles between primary and secondary HLH have not been compared. The aim of the study was to test whether the Th1/Th2 cytokine profile could be used as a tool to differentiate between primary and secondary HLH. Methods: A total of 45 hospitalized Chinese children with HLH during the period of February 2010 through September 2012 were enrolled in the study. Fifty healthy children were enrolled as controls. Primary HLH related genes were sequenced using genomic DNA samples. The Th1/Th2 cytokine levels including interferon-γ (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10, IL-6, IL-4 and IL-2 were quantitatively determined by cytometric bead assay techniques. Results: Primary HLH group (n = 4) included one patient with biallelic heterozygous mutations in PRF1 gene, and three patients with hemizygous mutation in SH2D1A gene. Based on the available genetic data, the other 41 patients were classified into the secondary HLH group. When compared the cytokine levels between the two groups, IL-4 level in primary-HLH was significantly lower than that in secondary HLH (P = 0.025), while IFN-γ level in primary HLH had a tendency of statistically lower than that in secondary HLH (P= 0.051). Area under receiver operating characteristic (ROC) curves of IL-4 and IFN-γ, IL-10, TNF-α, IL-2, and IL-6 levels were 0.841, 0.799, 0.506, 0. 494, 0.457, and 0.250, respectively. ROC curves showed that 1.7 pg/ml of IL-4 had sensitivity and specificity for differentiation between primary and secondary HLH as 70.7 and 100.0 %, while 433.9 pg/ml of IFN-γ had sensitivity and specificity as 51.2 and 100.0 %, respectively. Conclusions: HLH patients with lower IL-4 and IFN-γ levels have higher possibility to be primary HLH. The cytokine profile may be used as an additional tool for the quick differential diagnosis between primary and secondary HLH. [ABSTRACT FROM AUTHOR]

Background Hand, foot and mouth disease (HFMD), a virus-induced infectious disease that usually affects infants and children, has an increased incidence in China in recent years. This study attempted to investigate the role of the Notch signaling pathway in the pathogenesis of HFMD. Methods Eighty-two children diagnosed with HFMD were enrolled into this study. The HFMD group was further divided into the uncomplicated HFMD and HFMD with encephalitis groups. The control group included 40 children who underwent elective surgery for treatment of inguinal hernias. Results Children with HFMD displayed significantly reduced CD3+, CD3+CD4+ and CD3+CD8+ cell subsets, but substantially enhanced CD3-CD19+ cell subset (p < 0.05 versus control subjects). The expression levels of Notch ligands Dll1 and Dll4 in the peripheral blood of the HFMD group were significantly higher than those in the control group (p < 0.05). There were statistically significant differences in CD3+, CD3+CD4+ and CD3-CD19+ cell subsets, but not in Notch ligand expression, between the uncomplicated HFMD and HFMD with encephalitis groups. Dll4 expression in HFMD subjects correlated negatively with the CD3+ and CD3+CD8+ cell subsets (p < 0.05), but positively with the CD3-CD19+ cell subset (p < 0.05). Furthermore, Dll4 expression in HFMD with encephalitis subjects correlated positively with total white blood cell (WBC) counts and total protein contents in cerebrospinal fluid (CSF) (p < 0.05). Conclusions The Notch ligand Dll4 exhibits a strong correlation with the CD3+, CD3+CD8+ and CD3-CD19+ cell subsets in children with HFMD, indicating that the Notch signaling may be involved in the development of HFMD by affecting the number and status of peripheral lymphocytes. [ABSTRACT FROM AUTHOR]

The article presents a case-controlled study that analyzes the relationship between single nucleotide polymorphisms (SNPs) in inducible costimulator (ICOS) genes and occurrence of breast cancer in Chinese women. It is mentioned that ICOS facilitates T-cells proliferation and its abnormal expression disturbs immune response poses the risk of cancer. It is observed that gene polymorphism of ICOS is associated with breast cancer and certain SNPs are related with breast cancer in Chinese women.