scholarly journals Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review

2010 ◽  
Vol 222 (4) ◽  
pp. 350-366 ◽  
Author(s):  
Katsuhiko Nosho ◽  
Yoshifumi Baba ◽  
Noriko Tanaka ◽  
Kaori Shima ◽  
Marika Hayashi ◽  
...  
2018 ◽  
Vol 143 (8) ◽  
pp. 2008-2016 ◽  
Author(s):  
Edward S. Taylor ◽  
John L. McCall ◽  
Shirley Shen ◽  
Adam Girardin ◽  
Fran M. Munro ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Lu ◽  
Qiaohong Zhang ◽  
Longyi Zhang

Background and AimsColorectal cancer (CRC) lacks obvious symptoms in the early stage of the disease, making it is easy to be misdiagnosed and remain undetected. Here, we explored the role of CD4+ memory stem T cells (TSCM) in peripheral blood in the early screening and auxiliary diagnosis of CRC.Materials and MethodsPatients diagnosed with a “colorectal mass” by colonoscopy, at the Dongyang People’s Hospital (Zhejiang, China), between November 2020 and June 2021, were included in this prospective study. Using histopathological results as the gold standard for diagnosis, patients were divided into “CRC group” and “benign tumor group”. Healthy volunteers were recruited as “healthy controls.” Ten-color flow cytometry was used to detect CD4+ T cell subsets, and the results were analyzed using the Kaluza software. Carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) were detected by the Roche Cobas e 602 electrochemiluminescence immunoassay analyzer.ResultsThis study involved 33 patients with CRC, 41 patients with colorectal benign tumors, and 49 healthy volunteers. The absolute value and frequency of CD4+ TSCM can clearly distinguish colorectal cancer, benign tumors, and healthy controls. According to the area under the receiver operating characteristic curve (AUC), the absolute value of CD4+ TSCM used to assist in the diagnosis of CRC was 0.758 (sensitivity: 0.612; specificity: 0.788), which is higher than the values for CEA (AUC: 0.707) and CA199 (AUC: 0.552). In early screening, the sensitivity of the absolute value of CD4+ TSCM (sensitivity: 0.612) was significantly higher than that of CEA (sensitivity: 0.333) and CA199 (sensitivity: 0.259).ConclusionCD4+ TSCM in peripheral blood may be a promising immune index for the early screening and auxiliary diagnosis of CRC.


2019 ◽  
Vol 10 ◽  
Author(s):  
Salman M. Toor ◽  
Khaled Murshed ◽  
Mahmood Al-Dhaheri ◽  
Mahwish Khawar ◽  
Mohamed Abu Nada ◽  
...  

2012 ◽  
Vol 279 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Martin Scurr ◽  
Awen Gallimore ◽  
Andrew Godkin

2002 ◽  
Vol 127 (1) ◽  
pp. 85-91 ◽  
Author(s):  
S. J. C. Golby ◽  
C Chinyama ◽  
J Spencer

Medicine ◽  
2019 ◽  
Vol 98 (41) ◽  
pp. e17525 ◽  
Author(s):  
Najib Aziz ◽  
Beth D. Jamieson ◽  
Joshua J. Quint ◽  
Otoniel Martinez-Maza ◽  
Marianne Chow ◽  
...  

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A435-A435
Author(s):  
Richard Kim ◽  
Minal Barve ◽  
Hirva Mamdani ◽  
Melissa Johnson ◽  
Byung Ha Lee ◽  
...  

BackgroundCheckpoint inhibitor (CPI) monotherapy is ineffective for microsatellite stable colorectal cancer (MSS-CRC). NT-I7 (efineptakin alfa) is the first-in-class long-acting IL-7 that can increase T-cell infiltration in the tumor microenvironment (TME). We hypothesize that NT-I7 may create a favorable immune-reactive TME to enhance the efficacy of CPI when combined with pembrolizumab (pembro).MethodsThis is an open-label, phase 2a study in subjects with relapsed/refractory (R/R) tumors, including CPI-naïve R/R MSS-CRC. Subjects received the recommended-phase-2-dose of NT-I7 intramuscularly at 1200 µg/kg every 6 weeks (Q6W) plus pembro 200 mg intravenously Q3W. Preliminary anti-tumor activity based on Overall Response Rate (ORR) was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as a primary objective and by iRECIST as an exploratory objective. Biomarker analyses in peripheral blood and tumor biopsies were performed.ResultsAs of 15-July-2021, 19 subjects were enrolled in the CPI-naïve R/R MSS-CRC cohort. Six subjects are ongoing. Median age 58 years [37–81], ECOG PS 0 (26%), 1 (74%). Sixteen (84%) subjects received ≥ 2 prior therapies. All subjects had metastatic or locally advanced disease at enrollment. The median duration of follow-up was 4.64 months. Among 15 evaluable subjects, disease-control rate (DCR) based on RECIST1.1 was 47% and 1 subject achieved partial response per iRECIST (iPR) with 33% tumor reduction. Treatment-related adverse events (AEs) occurred in 14 (73.7%) subjects, 9 (47.4%) G1–2 events and 5 (26.3%) G3 events; no G4 or G5 AEs were reported. No subjects discontinued from the study due to AE. NT-I7 + pembro elicited a significant increase in the absolute lymphocyte count that peaked at week 3 (>3X from baseline, p<0.0001) and was sustained at least until week 18. CD4+/CD8+ T-cell subsets followed the same response pattern. Importantly, Stem-Cell Memory CD8+ T-cells (TSCM), the potential target for CPIs that differentiate into effectors, were remarkably increased post-study treatment (>25X from baseline, p<0.01). Plasmatic chemokines (CXCL9, CXCL10, CXCL11 and CCL9) were significantly increased after the first dose. The iPR subject had an enhanced T-cell infiltration in the TME at week 5. Subject’s follow-up continues and more updated data will be presented.ConclusionsThe chemo-free combination of NT-I7 + pembro was well tolerated and showed encouraging anti-tumor activity in subjects with CPI-naïve R/R MSS-CRC. Increased TSCM and CD8+ T-cell infiltration in TME may be the underlying mechanisms of action for the observed efficacy. These results support continued evaluation of NT-I7 + pembro in CPI-naïve subjects with R/R MSS-CRC.AcknowledgementsThe authors thank ICON for their partnership in conducting this trial.Trial RegistrationNCT04332653Ethics ApprovalThe trial was approved by MD Anderson IRB (#2020–0008_MOD001), Mary Crowley IRB (#20–13) and Advarra IRB (#Pro00042639)All participant gave informed consent prior to study enrollment.


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