scholarly journals Cancer-Associated Fibroblast Subgroups Showing Differential Promoting Effect on HNSCC Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 654
Author(s):  
Soo Hyun Kang ◽  
Su Young Oh ◽  
Heon-Jin Lee ◽  
Tae-Geon Kwon ◽  
Jin-Wook Kim ◽  
...  

Background: The critical effect of the tumor microenvironment on cancer progression is well recognized. Recent research suggests that the cancer-promoting properties of the tumor stroma may be attributed to fibroblasts. However, the effect of cancer-associated fibroblast (CAF) on the progression of head and neck squamous cell carcinoma (HNSCC) is not well known. Methods: From the immunohistochemical analysis of head and neck squamous cell carcinoma (HNSCC) tissues, we divided CAF into two groups depending on the presence or absence of a well-demarcated boundary between epithelial cancer cells and the surrounding extracellular matrix (ECM). Primary culture of CAF was performed, followed by co-transplantation with HNSCC cells into mice oral mucosa, and the tumorigenesis was compared. The mRNA expression patterns between these two CAF groups were compared using DNA microarray analysis. Results: CAFs from cancer tissues that showed no demarcation between ECM and epithelial cancer cells (CAF-Promote) tended to stimulate Matrigel invasion of HNSCC cells. Conversely, CAFs from cancer tissues that showed a boundary with epithelial cancer cells (CAF-Delay) caused no remarkable increase in Matrigel invasion. Compared with CAF-P, CAF-D is less effective in promoting FaDu tumorigenicity in the mouse model. In DNA microarray analysis, COL3A1 and COL6A6 showed particularly high expression in the CAF-D group. Conclusions: These cancer stroma-derived collagen proteins might delay the HNSCC progression. These findings are expected to provide vital information for predicting HNSCC prognosis and developing drug targets in the future.

2003 ◽  
Vol 129 (7) ◽  
pp. 760 ◽  
Author(s):  
John C. Sok ◽  
M. Abraham Kuriakose ◽  
Vinit B. Mahajan ◽  
Aaron N. Pearlman ◽  
Mark D. DeLacure ◽  
...  

2015 ◽  
Vol 89 (15) ◽  
pp. 7944-7954 ◽  
Author(s):  
Marlena M. Westcott ◽  
Jingfang Liu ◽  
Karishma Rajani ◽  
Ralph D'Agostino ◽  
Douglas S. Lyles ◽  
...  

ABSTRACTOncolytic viruses (OV) preferentially kill cancer cells due in part to defects in their antiviral responses upon exposure to type I interferons (IFNs). However, IFN responsiveness of some tumor cells confers resistance to OV treatment. The human type I IFNs include one IFN-β and multiple IFN-α subtypes that share the same receptor but are capable of differentially inducing biological responses. The role of individual IFN subtypes in promoting tumor cell resistance to OV is addressed here. Two human IFNs which have been produced for clinical use, IFN-α2a and IFN-β, were compared for activity in protecting human head and neck squamous cell carcinoma (HNSCC) lines from oncolysis by vesicular stomatitis virus (VSV). Susceptibility of HNSCC lines to killing by VSV varied. VSV infection induced increased production of IFN-β in resistant HNSCC cells. When added exogenously, IFN-β was significantly more effective at protecting HNSCC cells from VSV oncolysis than was IFN-α2a. In contrast, normal keratinocytes and endothelial cells were protected equivalently by both IFN subtypes. Differential responsiveness of tumor cells to IFN-α and -β was further supported by the finding that autocrine IFN-β but not IFN-α promoted survival of HNSCC cells during persistent VSV infection. Therefore, IFN-α and -β differentially affect VSV oncolysis, justifying the evaluation and comparison of IFN subtypes for use in combination with VSV therapy. Pairing VSV with IFN-α2a may enhance selectivity of oncolytic VSV therapy for HNSCC by inhibiting VSV replication in normal cells without a corresponding inhibition in cancer cells.IMPORTANCEThere has been a great deal of progress in the development of oncolytic viruses. However, a major problem is that individual cancers vary in their sensitivity to oncolytic viruses. In many cases this is due to differences in their production and response to interferons (IFNs). The experiments described here compared the responses of head and neck squamous cell carcinoma cell lines to two IFN subtypes, IFN-α2a and IFN-β, in protection from oncolytic vesicular stomatitis virus. We found that IFN-α2a was significantly less protective for cancer cells than was IFN-β, whereas normal cells were equivalently protected by both IFNs. These results suggest that from a therapeutic standpoint, selectivity for cancer versus normal cells may be enhanced by pairing VSV with IFN-α2a.


2020 ◽  
Vol 19 (3) ◽  
pp. 171-178
Author(s):  
Masatoshi Suzuki ◽  
Chen Wang ◽  
Fengzhu Zhang ◽  
Ujjal K. Bhawal ◽  
Hidenori Yamaguchi ◽  
...  

2012 ◽  
Vol 75 (6) ◽  
pp. 1803-1815 ◽  
Author(s):  
Koji Katada ◽  
Takeshi Tomonaga ◽  
Mamoru Satoh ◽  
Kazuyuki Matsushita ◽  
Yurie Tonoike ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Fan Yang ◽  
Ziqing Zeng ◽  
Jing Li ◽  
Xiubao Ren ◽  
Feng Wei

Background: T-cell Immunoglobulin and Mucin domain-containing molecule-3 (TIM-3) is a new immune checkpoint molecule which plays important and complex roles in regulating immune responses and in inducing immune tolerance. TIM-3 is expressed on activated T cells and its signaling on cytotoxic T cells leads to T cell exhaustion which is mediated by carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on tumor tissues and/or tumor infiltrating lymphocytes (TILs).Methods: In the present study, we investigated TIM-3 and CEACAM1 immunohistochemical expression in 80 head and neck squamous cell carcinoma (HNSCC) specimens, linked to detailed outcome, clinic-pathological parameters. Here we reported scores and absolute counts of TIM-3+/CEACAM1+ TILs, and evaluated the expression of CEACAM1 on tumor tissues.Results: The results showed that more TIM-3+ TILs infiltration correlated with poorer overall survival (p < 0.001), as did the presence of CEACAM1 on cancer cells (p < 0.001) and CEACAM1+ TILs in tumor microenvironment (p = 0.015). Multivariate Cox regression analysis revealed that high TIM-3+ TILs may be considered as an independent prognostic factor of poor disease outcome (hazard ratio, 2.066; 95% confidence interval, 1.027–4.159; p = 0.042), as well as cancer cells expressed CEACAM1 level (hazard ratio, 5.885; 95% confidence interval, 2.832–12.230; p < 0.001).Conclusion: Our results indicate that expression of TIM-3 and CEACAM1 may represent a highly dysfunctional population of T cells. Our current findings suggest both of them were valuable predicting markers that might provide help for clinicians to design effective immunotherapeutic regimen against head and neck carcinoma.


Sign in / Sign up

Export Citation Format

Share Document