Evaluation of antigen specific recognition and cell mediated cytotoxicity by a modified lysispot assay in a rat colon carcinoma model

Bordignon, Valentina; Cordiali‐Fei, Paola; Rinaldi, Monica; Signori, Emanuela; Cottarelli, Andrea; Zonfrillo, Manuela; Ensoli, Fabrizio; Rasi, Guido; Fuggetta, Maria Pia

doi:10.1186/1756-9966-31-9

Cited by 9 publications

(4 citation statements)

References 40 publications

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“…[32][33][34][35] In contrast with IFN-γ production, administration of NvC-M2ex1, NvC-M2ex3, and NvC-M2ex5 resulted in a significant decrease in IL-10, suggesting a type 1 T helper immune response.…”

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confidence: 99%

Potential recombinant vaccine against influenza A virus based on M2e displayed on nodaviral capsid nanoparticles

Yong¹,

Yeap²,

Ho³

et al. 2015

IJN

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Influenza A virus poses a major threat to human health, causing outbreaks from time to time. Currently available vaccines employ inactivated viruses of different strains to provide protection against influenza virus infection. However, high mutation rates of influenza virus hemagglutinin (H) and neuraminidase (N) glycoproteins give rise to vaccine escape mutants. Thus, an effective vaccine providing protection against all strains of influenza virus would be a valuable asset. The ectodomain of matrix 2 protein (M2e) was found to be highly conserved despite mutations of the H and N glycoproteins. Hence, one to five copies of M2e were fused to the carboxyl-terminal end of the recombinant nodavirus capsid protein derived from Macrobrachium rosenbergii . The chimeric proteins harboring up to five copies of M2e formed nanosized virus-like particles approximately 30 nm in diameter, which could be purified easily by immobilized metal affinity chromatography. BALB/c mice immunized subcutaneously with these chimeric proteins developed antibodies specifically against M2e, and the titer was proportional to the copy numbers of M2e displayed on the nodavirus capsid nanoparticles. The fusion proteins also induced a type 1 T helper immune response. Collectively, M2e displayed on the nodavirus capsid nanoparticles could provide an alternative solution to a possible influenza pandemic in the future.

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confidence: 99%

Potential recombinant vaccine against influenza A virus based on M2e displayed on nodaviral capsid nanoparticles

Yong¹,

Yeap²,

Ho³

et al. 2015

IJN

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“…Many methods based on radioactivities, enzyme-linked immunospot, and flow cytometry have been developed to evaluate the efficacy of CTL-mediated tumor rejection both in vitro and in vivo. In these methods, anticancer immune www.nature.com/scientificreports/ responses are quantitatively determined from information either associated with lysis of target cells, or related to engagement of pathways specific for cytotoxicity [43][44][45] . However, none of these approaches allows investigation of CTL-mediated tumor rejection in contexts mimicking the physical constraints in tumor interstitium, which is characterized by narrow entrances confined by dense collagenous capsule and high IFP that both physically impede CTL infiltration.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of cytotoxic T lymphocyte-mediated anticancer response against tumor interstitium-simulating physical barriers

Chen

Wang

et al. 2020

Sci Rep

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Tumor antigen-specific cytotoxic T lymphocyte (CTL) is a promising agent for cancer therapy. Most solid tumors are characterized by increased interstitial fluid pressure (IFP) and dense collagen capsule, which form physical barriers to impede cancer treatment. However, it remains unclear how CTL-mediated anticancer response is affected at the presence of these obstacles. Using a microfluidic-based platform mimicking these obstacles, we investigated the migration characteristics and performance of anticancer response of CTLs targeting hepatic cancer cells via antigen-specific and allogeneic recognition. The device consisted of slit channels mimicking the narrow interstitial paths constrained by the fibrous capsule and increased IFP was simulated by applying hydrostatic pressure to the tumor center. We found that antigen-specificity of CTLs against the targeted cancer cells determined the cytotoxic efficacy of the CTLs but did not significantly affect the success rate in CTLs that attempted to infiltrate into the tumor center. When increased IFP was present in the tumor center, CTL recruitment to tumor peripheries was promoted but success of infiltration was hindered. our results highlight the importance of incorporating the physical characteristics of tumor interstitum into the development of CTL-based cancer immunotherapy. Tumor antigen-specific CD8 + cytotoxic T lymphocyte (CTL)-mediated killing of tumor cells has a crucial role in cancer immunotherapy 1. Success of CTL-mediated tumor rejection requires the recruitment, infiltration, and expansion of tumor antigen-specific CTLs in tumor interstitium-the fluidic and matrix compartments between vessels and tumor cells, and recognition and killing of the tumor cells by the CTLs 2. However, a large body of evidence indicates that tumor cells actively reprogram surrounding interstitium to restrict CTLs from interacting with the tumor cells 3. For example, many types of cancer upregulate endothelins signalling of tumor endothelium to impede CTLs infiltration in tumor 4,5 ; soluble mediators such as IL-10 and transforming growth factor β (TGF-β) secreted by either tumor cells or tumor-recruited Treg cells significantly suppress the cytotoxic function of CTLs 3. While a multitude of chemical factors employed by cancers to escape from anticancer immunity are disclosed 6 , an increasing interest has recently been gained in the physical barriers established by tumors in their interstitium, which also poses a significant challenge to CTLs to successfully contact the targeting cells 7,8. Direct delivery of immune cells into tumor interior via perfusion may be physically hindered by the increased vascular resistance imposed by the high compressive stress generated by tumor growth 9,10. The growth-induced solid stress is mainly contributed by the collagen network and space-taking molecules, such as hyaluronan, accumulated in the tumor interstitium 11. Strategies to improve the delivery of blood-borne therapeutic agents against tumor, including the anticancer immune cells, has ...

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“…Dysfunction of DNA repair systems may make a significant contribution (Masutani et al, 2003). CRC is a common and complex multifactorial disease in which environmental and host-related factors interact (Bordignon et al, 2012;Petraki et al, 2012;Wang et al, 2013). Data has indicated an association of the descent productivity of DNA repair and the increased susceptibility of colorectal cancer (Jiricny and Marra, 2003).…”

Section: Discussionmentioning

confidence: 99%

Genetic Association between ERCC5 rs17655 Polymorphism and Colorectal Cancer Risk: Evidence Based on a Meta-analysis

Zeng

Li²,

Wang³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Previous studies evaluating the association between the excision repair cross complementing group 5 (ERCC5) gene rs17655 polymorphism and colorectal cancer susceptibility generated controversial results. To generate large-scale evidence on whether the ERCC5 rs17655 polymorphism might indeed be associated with colorectal cancer susceptibility, the present meta-analysis was performed. Materials and Methods: Data were collected from PubMed, Embase and Web of Science, with the last report up to Apr 03, 2015. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of any association. Results: A total of nine studies including 5,102 cases and 6,326 controls based on the search criteria were included and significant associations were found between ERCC5 rs17655 polymorphism CG vs GG overall (OR = 1.29, 95% CI =1.18~1.40) and in the dominant model (OR=1.23, 95% CI =1.13~1.33). On subgroup analysis by ethnicity and source of controls, the ERCC5 rs17655 polymorphism was found to correlate with the pathogenesis of colorectal cancer among Asians and Caucasians and with hospital-based populations. Conclusions: This meta-analysis suggests that the ERCC5 rs17655 polymorphism might contribute to genetic susceptibility to colorectal cancer.

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Evaluation of antigen specific recognition and cell mediated cytotoxicity by a modified lysispot assay in a rat colon carcinoma model

Cited by 9 publications

References 40 publications

Potential recombinant vaccine against influenza A virus based on M2e displayed on nodaviral capsid nanoparticles

Potential recombinant vaccine against influenza A virus based on M2e displayed on nodaviral capsid nanoparticles

Evaluation of cytotoxic T lymphocyte-mediated anticancer response against tumor interstitium-simulating physical barriers

Genetic Association between ERCC5 rs17655 Polymorphism and Colorectal Cancer Risk: Evidence Based on a Meta-analysis

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