scholarly journals CD8+ T Cell Densities and Stromal PD-L1 but not Tumoral PD-L1 Associated with Favorable Prognosis in Schistosomal Colorectal Cancer

2021 ◽  
Author(s):  
Weixia Wang ◽  
Hongyan Jing ◽  
Jican Liu ◽  
Dacheng Bu ◽  
Yingyi Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Independent Predictor ◽  
Immunohistochemical Analysis ◽  
Prognosis Factor ◽  
Independent Predictive Factor ◽  
Favorable Prognosis ◽  
Total Cohort ◽  
Cell Densities ◽  
And Gender

Abstract Backgroud: It was known that the expression of programmed cell death-ligand 1 (PD-L1) was correlated with CD8+ T cells, which could produce IFNγ. The effect of infection of Schistosoma japonicum on CD8+ T cells and then on PD-L1 expression was unknown and the utility of CD8+ TILs as a biomarker for schistosomal CRC (SCRC) has rarely been reported. Methods: A total of 338 patients with CRC were enrolled. Immunohistochemical analysis was conducted to evaluate the expression of PD-L1, infiltration by CD8+ T cells. Results: In the total cohort, results showed that CD8+ TIL density was positively correlated with tumoral and stromal PD-L1 expression (p＜0.05). But there were no correlation between schistosomiasis and CD8+ TILs and PD-L1. Furthermore, CD8+ TIL density, schistosomiasis, TNM stage, lymph nodes positive for CRC and gender were independent predictive factors for overall survival (OS) (p＜0.05). Stromal PD-L1(sPD-L1) but not tumoral PD-L1(tPD-L1) expression was correlated with OS but it was not an independent predictor (p=0.046). In patients without schistosomiasis, CD8+T cells and sPD-L1 were associated with better OS (p＜0.05). In patients with schistosomiasis, CD8+T cells were independent prognosis factor (p=0.05). Conclusions: The study showed that CD8+ TILs was an independent predictive factor for OS in CRC and SCRC patients. The expression of PD-L1 was positively associated with CD8+TILs density. There were no correlation between schistosomiasis and CD8+TILs and PD-L1. Stromal PD-L1 but not tPD-L1 was significantly associated with OS, whereas it was not an independent prognostic factor.

scholarly journals CD8+ T cell densities and PD-L1 associated with favorable prognosis in schistosomiasis-associated Colorectal Cancer

2021 ◽  
Author(s):  
Weixia Wang ◽  
Hongyan Jing ◽  
Jican Liu ◽  
Yingyi Zhang ◽  
Ting Zhu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Cd8 T Cells ◽  
Independent Predictor ◽  
Immunohistochemical Analysis ◽  
Predictive Biomarker ◽  
Independent Predictive Factor ◽  
Cell Densities ◽  
And Gender ◽  
Infiltrating Lymphocytes

Abstract Backgroud: The expression of programmed cell death-ligand 1 (PD-L1) was correlated with CD8+ T cells, which could producing IFNγ. The effect of infection of Schistosoma japonicum on CD8+ tumour-infiltrating lymphocytes (TILs) and then on PD-L1 expression has rarely been reported and the utility of CD8+ TILs as a biomarker for colorectal cancer (CRC), especially for schistosomal CRC, are still controversial and needing to be determined in CRC. Methods: A total of 338 patients with CRC were enrolled in this study. Immunohistochemical analysis were performed to evaluated the expression of PD-L1 within tumor cells (tPD-L1) and within stromal cells (sPD-L1), infiltration by CD8+ T cells. Results: In the whole cohort, results showed that CD8+ TIL density was positively correlated with tumoral and stromal PD-L1 expression （p＜0.05）. But there were no correlation between schistosomiasis and PD-L1 and CD8+ TILs. Furthermore, CD8+ TIL density, schistosomiasis, TNM stage, lymph nodes positive for CRC and gender were significantly independent predictive factors for overall survival (OS)（p＜0.05）. Stromal PD-L1 but not tPD-L1 expression was correlated with OS but was not an independent predictor (p=0.046). In patients without schistosomiasis, sPD-L1 was significantly associated with better OS but was not an independent predictor（p =0.004）.However, there were no association between schistosomiasis and OS in patients with schistosomal ifection. Conclusions: Our analysis indicated that CD8+ was an independent predictive factor for OS. And the expression of PD-L1 was positively associated with CD8+ TILs density. There were no correlation between schistosomiasis and PD-L1 and CD8+ TILs. Stromal PD-L1 but not tPD-L1 was significantly associated with OS, but was not an independent prognostic factor. It is proposed that PD-L1 expression in combination with CD8+ TIL could be a useful predictive biomarker in CRC patients.

scholarly journals Correlation between schistosomiasis and CD8+ T cell and stromal PD-L1 as well as the different prognostic role of CD8+ T cell and PD-L1 in schistosomal-associated colorectal cancer and non-schistosomal-associated colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Weixia Wang ◽  
Hongyan Jing ◽  
Jican Liu ◽  
Dacheng Bu ◽  
Yingyi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Independent Predictor ◽  
Immunohistochemical Analysis ◽  
Cd8 T Cell ◽  
Prognosis Factor ◽  
Independent Predictive Factor

Abstract Background The effect of schistosomiasis on CD8+ T cells and then on PD-L1 expression was unknown, and the utility of CD8+ TILs as a biomarker for schistosomal-associated colorectal cancer (SCRC) rarely has been reported. Methods Three hundred thirty-eight patients with colorectal cancer (CRC) were enrolled. Immunohistochemical analysis was conducted to evaluate the expression of PD-L1 and the infiltration of CD8+ T cells. Results In the total cohort, the results showed that CD8+ TIL density was positively correlated with tumoral (p = 0.0001) and stromal PD-L1 expression (p = 0.0102). But there were no correlation between schistosomiasis and CD8+ TILs and PD-L1. Furthermore, CD8+ TIL density (p = 0.010), schistosomiasis (p = 0.042) were independent predictive factors for overall survival (OS). Stromal PD-L1 (sPD-L1) was correlated with OS (p = 0.046), but it was not an independent predictor. In patients without schistosomiasis, CD8 + T cells (p = 0.002) and sPD-L1 (p = 0.005) were associated with better OS. In patients with schistosomiasis, CD8 + T cells were independent prognosis factor (p = 0.045). Conclusions The study showed that CD8+ TILs was an independent predictive factor for OS in CRC and SCRC patients. The expression of PD-L1 was positively associated with CD8 + TILs density. There were no correlation between schistosomiasis and CD8 + TILs and PD-L1. Stromal PD-L1 but not tPD-L1 was significantly associated with OS, whereas it was not an independent prognostic factor.

Mutated Nucleophosmin 1 (NPM1) Is an Immunogenic Target and Patients with NPM1mut Acute Myeloid Leukemia (AML) Showed High Expression of Different Leukemia-Associated Antigens (LAAs)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3592-3592
Author(s):  
Susanne Hofmann ◽  
Vanessa Schneider ◽  
Lars Bullinger ◽  
Yoko Ono ◽  
Anita Schmitt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Microarray Analysis ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
High Expression ◽  
Chromium Release ◽  
Cell Responses ◽  
Favorable Prognosis

Abstract Abstract 3592 Nucleophosmin gene 1 mutations (NPM1mut) are one of the most frequent molecular alterations in AML and distinct immune responses might contribute to the favorable prognosis of AML patients with NPM1mut. Recently, we showed specific T cell responses of CD4+ and CD8+ T cells against epitopes derived from mutated regions of NPM1 (Greiner et al., Blood. 2012 May 16, Epub). In the present study, we investigated clinical parameters and the clinical outcome of NPM1mut AML patients in accordance to their immune responses against different NPM1 epitopes. Moreover, we examined the quantitative expression of different leukemia-associated antigens (LAAs) in NPM1mutAML patients. In ELISpot analysis of 33 healthy volunteers and 27 AML patients, we detected T cell responses of CD4+ and CD8+ T cells against epitopes derived from the mutated region of NPM1. We performed further tetramer assays against the most interesting epitopes and chromium release assays to show the cytotoxicity of peptide-specific T cells. Microarray analysis was performed to analyze the expression of different LAAs in NPM1mut and NPM1wtAML patients. Two epitopes (peptide #1 and #3) derived from NPM1mut induced CD8+ T cell responses. 33% of the NPM1mut AML patients showed immune responses against peptide #1 and 44% against peptide #3. NPM1mut AML patients showed a significantly higher frequency of T cell responses against peptide #3 in contrast to HVs (p=0.046), whereas for peptide #1 the frequency of T cell responses of AML NPM1mut patients and HVs was not significantly different. Specific lysis of pulsed T2 cells but also NPM1mut leukemic blasts was detected in chromium release assays. Therefore, overlapping peptides (OL) were analyzed in ELISpot assays and the peptide called OL8 showed favorable results to activate both CD8+ and CD4+ T cells. We performed survival analysis for these 33 NPM1mut patients analyzed by ELISpot comparing cases with or without specific T cell responses. Our data suggest a trend to a better overall survival (OS) for patients with specific T cell responses against peptide #1 or #3. However, the patient numbers are small and the data have to be interpreted carefully. Analyses with material from larger controlled clinical trials with a high number of patients with NPM1mut AML have to be performed. Our microarray analysis of 30 AML patients showed a high expression of different LAAs like RHAMM, WT-1 and BCL-2 in all subtypes of cells of NPM1mutAML patients, also in leukemic progenitor cells. This demonstrates that NPM1 is an AML subtype suitable for poly-targeted immunotherapeutic trials. Taken together, NPM1mut might constitute an interesting target structure for individualized immunotherapeutic approaches in NPM1mut AML patients. We hypothesize that immune responses to NPM1 mutation may contribute to the favorable prognosis. Disclosures: No relevant conflicts of interest to declare.

A High Number of CD8+ T Cells Infiltrated in NSCLC Tissues is Associated With a Favorable Prognosis

2010 ◽  
Vol 18 (1) ◽  
pp. 24-28 ◽  
Author(s):  
Xuewei Zhuang ◽  
Xiyan Xia ◽  
Chuanxin Wang ◽  
Fei Gao ◽  
Ningning Shan ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Favorable Prognosis

scholarly journals Simplified Admix Archaeal Glycolipid Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Enhances Protection from Murine Melanoma

Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 91 ◽  
Author(s):  
Felicity C. Stark ◽  
Gerard Agbayani ◽  
Jagdeep K. Sandhu ◽  
Bassel Akache ◽  
Charis McPherson ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Therapy ◽  
Cd8 T Cells ◽  
Checkpoint Inhibitor ◽  
Immunohistochemical Analysis ◽  
Entrapment Efficiency ◽  
Patient Specific ◽  
Melanoma Tumor ◽  
Attractive Option ◽  
Archaeal Lipids

Archaeosomes are liposomes composed of natural or synthetic archaeal lipids that when used as adjuvants induce strong long-lasting humoral and cell-mediated immune responses against entrapped antigens. However, traditional entrapped archaeosome formulations have only low entrapment efficiency, therefore we have developed a novel admixed formulation which offers many advantages, including reduced loss of antigen, consistency of batch-to-batch production as well as providing the option to formulate the vaccine immediately before use, which is beneficial for next generation cancer therapy platforms that include patient specific neo-antigens or for use with antigens that are less stable. Herein, we demonstrate that, when used in combination with anti-CTLA-4 and anti-PD-1 checkpoint therapy, this novel admixed archaeosome formulation, comprised of preformed sulfated lactosyl archaeol (SLA) archaeosomes admixed with OVA antigen (SLA–OVA (adm)), was as effective at inducing strong CD8+ T cell responses and protection from a B16-OVA melanoma tumor challenge as the traditionally formulated archaeosomes with encapsulated OVA protein. Furthermore, archaeosome vaccine formulations combined with anti-CTLA-4 and anti-PD-1 therapy, induced OVA-CD8+ T cells within the tumor and immunohistochemical analysis revealed the presence of CD8+ T cells associated with dying or dead tumor cells as well as within or around tumor blood vessels. Overall, archaeosomes constitute an attractive option for use with combinatorial checkpoint inhibitor cancer therapy platforms.

scholarly journals Identification of Cyclin B1 as a Shared Human Epithelial Tumor-Associated Antigen Recognized by T Cells

2001 ◽  
Vol 194 (9) ◽  
pp. 1313-1324 ◽  
Author(s):  
Henry Kao ◽  
Jarrod A. Marto ◽  
Thomas K. Hoffmann ◽  
Jeffrey Shabanowitz ◽  
Sydney D. Finkelstein ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
High Performance ◽  
Tumor Cell Line ◽  
Immunohistochemical Analysis ◽  
Cyclin B1 ◽  
Breast Adenocarcinoma ◽  
Epithelial Tumor ◽  
Hla A2.1

We eluted peptides from class I molecules of HLA-A2.1+ breast adenocarcinoma and loaded reverse phase high-performance liquid chromatography (HPLC) fractions onto dendritic cells to prime naive CD8+ T cells. Fractions that supported growth of tumor-specific cytotoxic T lymphocytes were analyzed by nano-HPLC micro-ESI tandem mass spectrometry. Six HLA-A2.1-binding peptides, four 9-mers (P1-P4) differing in the COOH-terminal residue, and two 10-mers (P5 and P6) with an additional COOH-terminal alanine, were identified in one fraction. Peptide sequences were homologous to cyclin B1. We primed CD8+ T cells from another HLA-A2.1+ healthy donor with synthetic peptides and generated P4-specific responses. We also detected memory T cells specific for one or more of these peptides in patients with breast cancer and squamous cell carcinomas of the head and neck (SCCHN). T cells from one patient, restimulated once in vitro, could kill the tumor cell line from which the peptides were derived. Immunohistochemical analysis of tumor lines and tissue sections showed cyclin B1 overexpression and aberrant localization in the cytoplasm instead of the nucleus. Sequencing genomic DNA and cDNA corresponding to P1–P6 region showed that differences in COOH-terminal residues were not due to either DNA mutations or errors in transcription, suggesting a high error rate in translation of cyclin B1 protein in tumors.

Lymphocytic vasculitis in X-linked lymphoproliferative disease

Blood ◽  
2001 ◽  
Vol 97 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Jan P. Dutz ◽  
Loralyn Benoit ◽  
Xiaoxia Wang ◽  
Douglas J. Demetrick ◽  
Anne Junker ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Systemic Vasculitis ◽  
Immunohistochemical Analysis ◽  
Lymphoproliferative Disease ◽  
Sh2 Domain ◽  
Clinical Criteria ◽  
Barr Virus ◽  
Epstein Barr

Abstract Systemic vasculitis is an uncommon manifestation of X-linked lymphoproliferative disease (XLP), a disorder in which there is a selective immune deficiency to Epstein-Barr virus (EBV). The molecular basis for XLP has recently been ascribed to mutations within SLAM-associated protein (SAP), an SH2 domain–containing protein expressed primarily in T cells. The authors describe a patient who died as a result of chronic systemic vasculitis and fulfilled clinical criteria for the diagnosis of XLP. Sequencing of this patient'sSAP gene uncovered a novel point mutation affecting the SH2 domain. The patient presented with virus-associated hemophagocytic syndrome (VAHS) and later had chorioretinitis, bronchiectasis, and hypogammaglobulinemia develop. He further developed mononeuritis and fatal respiratory failure. Evidence of widespread small and medium vessel vasculitis was noted at autopsy with involvement of retinal, cerebral, and coronary arteries as well as the segmental vessels of the kidneys, testes, and pancreas. Immunohistochemical analysis using antibodies to CD20, CD45RO, and CD8 revealed that the vessel wall infiltrates consisted primarily of CD8+ T cells, implying a cytotoxic T-lymphocyte response to antigen. EBV DNA was detected by polymerase chain reaction (PCR) in arterial wall tissue microdissected from infiltrated vessels further suggesting that the CD8+ T cells were targeting EBV antigens within the endothelium. The authors propose that functional inactivation of the SAP protein can impair the immunologic response to EBV, resulting in systemic vasculitis.

CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers

2003 ◽  
Vol 94 (11) ◽  
pp. 1003-1009 ◽  
Author(s):  
Osamu Wakabayashi ◽  
Koichi Yamazaki ◽  
Satoshi Oizumi ◽  
Fumihiro Hommura ◽  
Ichiro Kinoshita ◽  
...  
Keyword(s):  
T Cells ◽  
Cancer Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Cancer Stroma ◽  
Favorable Prognosis
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