The Interplay Between Neutrophils and CD8+ T Cells Improves Survival in Human Colorectal Cancer

e16013 Background: Different primary tumor sites could impact colorectal cancer (CRC)’s survival outcomes and treatment effects. Previous studies had found that gut micro-biome distributions were different between left and right colon cancer(LCC, RCC). Out study aimed to further investigate the association between micro-biome and T lymphocytes among different tumor sites of patients with metastatic CRC. Methods: Between April 2018 and Mars 2019, we enrolled 40 metastatic CRC patients in Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, China. We collected patients’ stool samples for micro-biome analysis by 16s rRNA sequencing approaches, as well as patients’ blood samples to analyses T lymphocyte subsets by flow cytometry methods. The study had been proved by ethics committee of Xiyuan Hospital (2016XLA122-1). All patients consented before enrollment. Results: Among 40 patients, 28% were female, with average age of 63±15 years old. There were 10 RCC, 9 LCC and 21 rectal cancer(RC) patients. Alpha diversity analysis showed that sobs index of the micro-biome of patients with RC and RC was significantly higher than whom were RCC(254.89±99, 247±89 versus.[vs.]101.17±51, p= 0.001). PCoA analysis on OTU level detected that first principal component[PC1] (26.24%) could be separated significantly between RCC and LCC( p= 0.048), as well as between RC and RCC (PC1,14.17%, p= 0.024). Community analysis showed that the proportion of Bacteroidetes was significantly higher in patients with RCC than whom with LCC and RC( p= 0.009). Conversely, the proportion of Firmicutes, Proteobacteria and Verrucomicrobia were higher in LCC patients than others( p= 0.37, 0.047 and 0.032 respectively). Canonical Correlation Analysis (CCA) analysis proved that the CD4+ and CD8+ T cells counts were environmental factors, which were significantly associated with certain micro-biome and samples from different tumor sites( p= 0.037 and 0.01 respectively). Trends showed that CD4+ T cells were positively related with samples of RC and bacteria parabacteroides and bifidobacterium, while CD8+ T cells were positively related with samples of RCC and bacteria Lachnospira, Sutterella and Bacteroides. Conclusions: In our study, we found that patients with LCC and RC had more beneficial gut micro-biome than whom with RCC. In addition, such difference might be associated with body T cell immunity.

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In situ analysis of FOXP3+ regulatory T cells and myeloid dendritic cells in human colorectal cancer tissue and tumor-draining lymph node

Biomedical Reports ◽

10.3892/br.2012.35 ◽

2012 ◽

Vol 1 (2) ◽

pp. 207-212 ◽

Cited By ~ 7

Author(s):

XIAO-DONG GAI ◽

CHUN LI ◽

YANG SONG ◽

YAN-MING LEI ◽

BAO-XUE YANG

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Dendritic Cells ◽

Lymph Node ◽

Cancer Tissue ◽

Human Colorectal Cancer ◽

Myeloid Dendritic Cells ◽

Draining Lymph Node ◽

Tumor Draining Lymph Node

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Cytotoxic CD8+ T cells and tissue resident memory cells in colorectal cancer based on microsatellite instability and BRAF status

World Journal of Clinical Oncology ◽

10.5306/wjco.v12.i4.238 ◽

2021 ◽

Vol 12 (4) ◽

pp. 238-248

Author(s):

James Wei Tatt Toh ◽

Angela L Ferguson ◽

Kevin J Spring ◽

Hema Mahajan ◽

Umaimainthan Palendira

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Microsatellite Instability ◽

Cd8 T Cells ◽

Memory Cells

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Molecular correlates of immune cytolytic subgroups in colorectal cancer by integrated genomics analysis

NAR Cancer ◽

10.1093/narcan/zcab005 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Constantinos Roufas ◽

Ilias Georgakopoulos-Soares ◽

Apostolos Zaravinos

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Cd8 T Cells ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Cytolytic Activity ◽

Immune Checkpoints ◽

Patient Responsiveness ◽

Immune Related Genes ◽

Integrated Genomics

Abstract Although immune checkpoint inhibition (ICI) has shown promising results in metastatic dMMR/MSI-H colorectal cancer (CRC), the majority of pMMR/MSS patients do not respond to such therapies. To systematically evaluate the determinants of immune response in CRC, we explored whether patients with diverse levels of immune cytolytic activity (CYT) have different patterns of chromothripsis and kataegis. Analysis of CRC genomic data from the TCGA, indicated an excess of chromothriptic clusters among CYT-low colon adenocarcinomas, affecting known cancer drivers (APC, KRAS, BRAF, TP53 and FBXW7), immune checkpoints (CD274, PDCD1LG2, IDO1/2 and LAG3) and immune-related genes (ENTPD1, PRF1, NKG7, FAS, GZMA/B/H/K and CD73). CYT-high tumors were characterized by hypermutation, enrichment in APOBEC-associated mutations and kataegis events, as well as APOBEC activation. We also assessed differences in the most prevalent mutational signatures (SBS15, SBS20, SBS54 and DBS2) across cytolytic subgroups. Regarding the composition of immune cells in the tumor milieu, we found enrichment of M1 macrophages, CD8+ T cells and Tregs, as well as higher CD8+ T-cells/Tregs ratio among CYT-high tumors. CYT-high patients had higher immunophenoscores, which is predictive of their responsiveness if they were to be treated with anti-PD-1 alone or in combination with anti-CTLA-4 drugs. These results could have implications for patient responsiveness to immune checkpoint inhibitors.

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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

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02433-w ◽

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.

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