scholarly journals CD44, a marker of cancer stem cells, is positively correlated with PD-L1 expression and immune cells infiltration in lung adenocarcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chenyue Zhang ◽  
Hui Wang ◽  
Xia Wang ◽  
Chenglong Zhao ◽  
Haiyong Wang

Abstract Background PD-L1 inhibitors is widely applied in lung adenocarcinoma patients. Tumor cells with high PD-L1 expression could trigger immune evasion. Cancer stem cells (CSCs) can evade from immunesurveillance due to their immunomodulating effects. However, the correlation between CSC and PD-L1 and some immune-related markers is seldom reported in patients with lung adenocarcinoma. Therefore, we aimed to ascertain their association in lung adenocarcinoma patients. Methods We assessed CD44 expression and its association with PD-L1 in lung adenocarcinoma, using Tumor Immune Estimation Resource (TIMER), which was further validated in our patient cohort. The immune cells infiltration was depicted by CIBERSORT using GEO database. The correlation between CD44 and immune cells was also analyzed. We further evaluated the prognostic role of CD44 in patients with lung adenocarcinoma both using Kaplan–Meier plotter and validated in our patient cohort. Results Positive association between CD44 and PD-L1 were found in lung adenocarcinoma patients. T cells CD4 memory resting cells and mast cells resting cells varied significantly between patients with CD44 high and those with CD44 low. Furthermore, positive association could be found between CD44 expression and immune cells. Arm-level depletion of CD44 was linked with B cell, CD4+ T cell, neutrophil and dendritic cell infiltration. Patients with higher CD44 levels had worsened overall survival (OS). Conclusions In summary, these results demonstrate that CD44 was associated with PD-L1 and infiltration of immune cells, and was a negative prognostic factor for predicting worsened OS in lung adenocarcinoma.

2020 ◽  
Author(s):  
Chenyue Zhang ◽  
Hui Wang ◽  
Xia Wang ◽  
Chenglong Zhao ◽  
Haiyong Wang

Abstract Background: PD-L1 inhibitors is widely applied in lung adenocarcinoma patients. Tumor cells with high PD-L1 expression could trigger immune evasion. Cancer stem cells (CSCs) can evade from immunesurveillance due to their immunomodulating effects. However, the correlation between CSC and PD-L1 and some immune-related markers is seldom reported in patients with lung adenocarcinoma. Therefore, we aimed to ascertain their association in lung adenocarcinoma patients. Methods: We assessed CD44 expression and its association with PD-L1 in lung adenocarcinoma, using Tumor Immune Estimation Resource (TIMER), which was further validated in our patient cohort. The immune cells infiltration was depicted by CIBERSORT using GEO database. The correlation between CD44 and immune cells was also analyzed. We further evaluated the prognostic role of CD44 in patients with lung adenocarcinoma both using Kaplan-Meier plotter and validated in our patient cohort. Results: Positive association between CD44 and PD-L1 were found in lung adenocarcinoma patients. T cells CD4 memory resting cells and mast cells resting cells varied significantly between patients with CD44 high and those with CD44 low. Furthermore, positive association could be found between CD44 expression and immune cells. Arm-level depletion of CD44 was linked with B cell, CD4+ T cell, neutrophil and dendritic cell infiltration. Patients with higher CD44 levels had worsened overall survival (OS). Conclusions: In summary, these results demonstrate that CD44 was associated with PD-L1 and infiltration of immune cells, and was a negative prognostic factor for predicting worsened OS in lung adenocarcinoma.


Author(s):  
Nese Unver

: Cancer stem cells represent a rare subpopulation of cancer cells carrying self-renewal and differentiation features in the multi-step tumorigenesis, tumor recurrence and metastasis. Pro-inflammatory stress is highly associated with cancer stemness via induction of cytokines, tumor-promoting immune cells and cancer stemness-related signaling pathways. This review summarizes the major pro-inflammatory factors affecting cancer stem cell characteristics and the critical immunotherapeutic strategies to eliminate cancer stem cells.


Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1293 ◽  
Author(s):  
Ghmkin Hassan ◽  
Masaharu Seno

The concepts of hematopoiesis and the generation of blood and immune cells from hematopoietic stem cells are some steady concepts in the field of hematology. However, the knowledge of hematopoietic cells arising from solid tumor cancer stem cells is novel. In the solid tumor microenvironment, hematopoietic cells play pivotal roles in tumor growth and progression. Recent studies have reported that solid tumor cancer cells or cancer stem cells could differentiate into hematopoietic cells. Here, we discuss efforts and research that focused on the presence of hematopoietic cells in tumor microenvironments. We also discuss hematopoiesis from solid tumor cancer stem cells and clarify the notion of differentiation of solid tumor cancer stem cells into non-cancer hematopoietic stem cells.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22230-e22230
Author(s):  
Y. Zhu ◽  
L. Chen

e22230 Background: There has been an increasing interest in recent years in the role stem cells play in health and disease. With an extensive understanding of their biology, a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs) has been confirmed in hematopoietic malignancies, brain cancer, and solid organ malignancies including breast, prostate, colon, and pancreatic cancer. Lung cancer is the leading cause of cancer mortality in most large cities of China. It is possible that lung cancer contains cancer stem cells responsible for its malignancy. The aim of this study is to identify, characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis. Methods: Side population (SP) cell analysis and sorting were applied to established human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting(FACS) was done. Stem cell properties of SP cells were evaluated by their proliferative index, colony-forming efficiency, tumorigenic potential, bi-differentiation capacity and the expression of common stem cell surface markers. Results: Lung cancer cells could grow in a serum-free Medium (SFM) as non-adherent spheres similar to neurospheres or mammospheres. The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers. SP cells had a greater proliferative index, a higher colony-forming efficiency and a greater ability to form tumor in vivo. SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive. Flow cytometric analysis of cell phenotyping showed that SP cells expressed CD133 and CD44, the common cell surface markers of cancer stem cells, while non-SP cells only expressed CD44. Conclusions: SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting. SP cells possessed the properties of cancer stem cells. No significant financial relationships to disclose.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e20547-e20547
Author(s):  
Alejandro Herreros-Pomares ◽  
Juan Diego de Maya ◽  
Héctor Amado ◽  
Cristóbal Aguilar-Gallardo ◽  
Eva Escorihuela ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21017-e21017
Author(s):  
Jinchun Wu ◽  
Xianyu Liu ◽  
Yanhua Mou ◽  
Shan Zeng ◽  
Jin Zhang ◽  
...  

e21017 Background: Lung adenocarcinoma (LUAD) occupies the most of non-small cell lung cancer (NSCLC) and shows promising response to PD-1 immunotherapy, but immune escape will cause treatment failure indicating poor prognosis. TWEAK (Tumor necrosis factor-related weak inducer of apoptosis, also known as TNFSF12) combining with its receptor FN14 (fibroblast growth factor–inducible 14) mediates crucial innate and adaptive immune pathways to promote the progression of multiple autoimmune diseases. So we assumed that TWEAK is a prognostic predictor and related with tumor-infiltrating immune cells (TIICs) in LUAD. Methods: TWEAK expression of LUAD was primarily investigated in The Cancer Immunome Atlas (TCIA) and then validated in Tumor Immune Estimation Resource (TIMER) databases. We assessed the effect of TWEAK on the survival via the Kaplan-Meier plotter, GEPIA2 (gene expression profiling interactive analysis) and PrognoScan databases. The relation between TWEAK and TIICs was explored in TIMER and TCIA, as well as the correlation of TWEAK and FN14 was analyzed in TIMER and GEPIA2. Results: Low TWEAK expression was significantly associated with poor relapse-free survival (RFS) (HR = 0.62, 95% CI = 0.4~0.97, logrank P = 0.035) and overall survival (OS) (HR = 0.61, 95% CI = 0.46~0.83, logrank P = 0.0012) in LUAD from Kaplan-Meier plotter. Similar impacts of TWEAK on the survival were validated in GEPIA2 and four independent cohorts from PrognoScan (jacob-00182-CANDF, GSE13213, jacob-00182-MSK and GSE31210). Moreover, reduced TWEAK expression was closely related with the paucity of TIICs which contributed to poor OS, including central memory CD8 T cells, plasmacytoid dendritic cells, activated CD8 T cells, monocytes, T follicular helper cells, immature B cells and eosinophils. In addition, TWEAK expression was positively related with the expression level of FN14 in both GEPIA2(R = 0.13, P= 0.0031) and TIMER (partial.cor = 0.212, P= 2.04e-06). Conclusions: Low TWEAK expression maybe indicate poor prognosis in LUAD, and correlated with the impaired infiltration of immune cells in the tumor region. The defective TWEAK/FN14 pathway possibly accounts for these observations, but the underlying mechanism needs to be further explored.


2016 ◽  
Vol 38 (6) ◽  
pp. 16-19
Author(s):  
Hisataka Kobayashi

Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cell-selective cancer therapy with enormous potential for treating cancer in a variety of ways. NIR-PIT not only kills cancer cells, but can also eliminate other unfavourable cells including cancer stem cells and immunosuppressor cells, among others, without damaging favourable cells such as immune cells, vascular cells and tissue stem cells. This technique can efficiently activate anti-tumour host immunity in a way that can even cure untreated distant metastasis.


Author(s):  
Martina Mang Leng Lei ◽  
Terence Kin Wah Lee

Cancer stem cells (CSCs) are subpopulations of undifferentiated cancer cells within the tumor bulk that are responsible for tumor initiation, recurrence and therapeutic resistance. The enhanced ability of CSCs to give rise to new tumors suggests potential roles of these cells in the evasion of immune surveillance. A growing body of evidence has described the interplay between CSCs and immune cells within the tumor microenvironment (TME). Recent data have shown the pivotal role of some major immune cells in driving the expansion of CSCs, which concurrently elicit evasion of the detection and destruction of various immune cells through a number of distinct mechanisms. Here, we will discuss the role of immune cells in driving the stemness of cancer cells and provide evidence of how CSCs evade immune surveillance by exerting their effects on tumor-associated macrophages (TAMs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), T-regulatory (Treg) cells, natural killer (NK) cells, and tumor-infiltrating lymphocytes (TILs). The knowledge gained from the interaction between CSCs and various immune cells will provide insight into the mechanisms by which tumors evade immune surveillance. In conclusion, CSC-targeted immunotherapy emerges as a novel immunotherapy strategy against cancer by disrupting the interaction between immune cells and CSCs in the TME.


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