Treatment of colon and breast carcinoma cells with 5‐fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA‐A(*)02.01 restricted, CEA‐peptide‐specific cytotoxic T cells <i>in vitro</i>

Correale, Pierpaolo; Aquino, Angelo; Giuliani, Alessandro; Pellegrini, Monia; Micheli, Lucia; Cusi, Maria Grazia; Nencini, Cristina; Petrioli, Roberto; Prete, Salvatore Pasquale; Vecchis, Liana De; Turriziani, Mario; Giorgi, Giorgio; Bonmassar, Enzo; Francini, Guido

doi:10.1002/ijc.10969

Cited by 80 publications

(60 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, we observed a significant decrease of MHC class I-positive cells after treatment with 5-FU and combinations. Our findings were different from what has been reported [23][24][25] where an increase in MHC class I on various epithelial tumor cells after treatment with 5-FU was described. We can only speculate why we observed an opposite effect.…”

Section: Discussioncontrasting

confidence: 99%

Synergistic effects of interferon-alpha in combination with chemoradiation on human pancreatic adenocarcinoma

Patrut²,

Schmidt³

et al. 2005

WJG

View full text Add to dashboard Cite

AIM:To determine whether IFN- is the agent that turns a slightly effective treatment (radiochemotherapy) into a potent therapy, we tested IFN- for its synergistic properties. METHODS:Eight pancreatic carcinoma cell lines were treated with the single agents and combinations of these. The role of IFN- regarding a) direct inhibitory effects; b) radio and chemosensitizing effects; c) anti-angiogenic properties and d) enhancement of immunogenicity was investigated. RESULTS:Our results show that IFN- has direct inhibitory properties and some synergistic influence as determined by AnnexinV/PI stain and cell count. IFN- is also able to prevent the increase in proliferation rate and VEGF secretion of CDDP resistant cells. Having taken the results from immunogenicity experiments together, we found cells that can be influenced by IFN- but were less susceptible against T cells. Furthermore, high expression of MHC molecules, CD118, EGF-R and Fas was predictive for a good response. CONCLUSION:In conclusion, IFN- has direct cytotoxic effects, acts as a radiosensitizer and circumvents tumor cell-regrowth after CDDP treatment. These mechanisms may be responsible for the good clinical outcome of CapRI.

show abstract

Section: Discussioncontrasting

confidence: 99%

Synergistic effects of interferon-alpha in combination with chemoradiation on human pancreatic adenocarcinoma

Patrut²,

Schmidt³

et al. 2005

WJG

View full text Add to dashboard Cite

show abstract

“…Particularly relevant was the sensitization of colon and breast carcinoma cells to antigenspecific CTLs after 5-FU treatment through increased expression of carcinoembryonic antigen and thymidylate synthetase antigens (CTL target antigens; refs. 40,41). Of note is the fact Fig.…”

Section: Discussionmentioning

confidence: 97%

Cytosine Deaminase-Uracil Phosphoribosyltransferase and Interleukin (IL)-12 and IL-18: A Multimodal Anticancer Interface Marked by Specific Modulation in Serum Cytokines

Khatri

Husaini²,

et al. 2009

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: To test the effects of a new combination, cytosine deaminase (CD) + uracil phosphoribosyltransferase (UPRT)^mediated gene-directed enzyme prodrug therapy (GDEPT) with interleukin (IL)-12 and IL-18, on (a) growth of murine prostate and remote tumor deposits, (b) mouse survival, and (c) T helper (Th) 1/Th2 serum cytokine balance with a special focus to assess correlation with tumor burden/survival. Experimental Design: Efficacy of intraprostatic administration of adenovirally delivered murine IL-12 and IL-18 against orthotopic RM1 tumors and lung pseudometastases was assessed in C57BL/6 mice. At necropsy, tumor growth, lung colony counts, effects on immune cell infiltration, vasculature, apoptosis, and proliferation were estimated. Next, CDUPRT-GDEPT + cytokines were tested at suboptimal doses in mice with RM1CDUPRT prostate tumors/RM1 lung deposits and analyzed as above. Effects on mouse survival were also assessed. Host immune responses to different treatments were assessed by monitoring 11serum cytokines using Luminex technology. Results: Our data show that IL-12 and IL-18, when combined with CDUPRT-GDEPT, caused significant reduction in local RM1 tumors and lung colonies with enhanced long-term survival versus individual treatments. A dramatic enhancement of tumor infiltration by a wider repertoire of immune cells and disruption of vasculature implied the combination to be more immunostimulatory and antiangiogenic. Remarkably, lowering of serum IL-4 and monocyte chemoattractant protein-1 (MCP-1) was consistently associated with lower tumor burden (local and systemic), and this, rather than an increase inTh1cytokines, better predicted treatment efficacy. In addition, mouse survival correlated with substantially higher cytokine (Th1/Th2) levels after treatment. Conclusion: Locoregional application of CDUPRT-GDEPTand IL-12/IL-18 was effective against local and systemic prostate cancer and improved survival. Monitoring serum levels of IL-4 and MCP-1may accurately reflect tumor burden and, hence, host response to therapy.Heterogeneity of clinical prostate cancer has culminated in inadequacy of single-treatment regimens and inefficient patient management. An urgent need has emerged for (a) new combination regimens that can be given into the primary tumor with systemic effects and without toxicities and (b) design of preclinical screening to generate clinically relevant data.Immunostimulatory strategies have the potential to combat cancer and generate long-term anticancer effects. However, poorly immunogenic tumors and immunocompromised patients pose a challenge. The in situ amplification of cytotoxicity via local and distant bystander effects by locally delivered gene-directed enzyme prodrug therapies (GDEPT) is shown to be inflammatory [T cells, macrophages, and natural killer (NK) cells], and several studies support the concept that further enhancement is possible using cytokines (1). This was first shown when IL-2 combined with thymidine kinasebased GDEPT (HSV-tk) was found to be more potent aga...

show abstract

“…5V -Aza-2V -deoxycytidine can reinduce the expression of these molecules on tumor cells in vitro thereby restoring melanoma-and renal cell carcinomaspecific CTL activity (27). Similarly, 5-FU restores CTL activity against treated colon and breast carcinoma cells (28). Some chemotherapeutics (melphalan and Mitomycin C) up-regulate the expression of costimulatory molecules (B7-1 and B7-2) thereby rendering the tumor cells themselves more efficient antigen presenting cells.…”

Section: Cytotoxic Chemotherapy Can Augment Tumor Vaccine Activitymentioning

confidence: 99%

Leveraging the Activity of Tumor Vaccines with Cytotoxic Chemotherapy

Emens¹,

Jaffee

2005

Cancer Research

162

View full text Add to dashboard Cite

Engaging the power of the patient's own immune system to actively seek out and destroy transformed cells holds great promise for cancer therapy. Tumor vaccines offer the potential for preventing cancer in high-risk individuals, preventing disease relapse after diagnosis and initial therapy, and shifting the balance of the host-tumor interaction to mitigate the progression of advanced cancers. The therapeutic activity of tumor vaccines is limited by the sheer physical burden of the cancer itself, pathways of local immune tolerance and escape active within the tumor microenvironment, and superimposed potent systemic mechanisms of immune tolerance. In this review, we describe how cytotoxic chemotherapy can be integrated with tumor vaccines using unique doses and schedules to break down these barriers, releasing the full potential of the antitumor immune response to eradicate disease. (Cancer Res 2005; 65(18): 8059-64)

show abstract

Treatment of colon and breast carcinoma cells with 5‐fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA‐A()02.01 restricted, CEA‐peptide‐specific cytotoxic T cells in vitro*

Cited by 80 publications

References 33 publications

Synergistic effects of interferon-alpha in combination with chemoradiation on human pancreatic adenocarcinoma

Synergistic effects of interferon-alpha in combination with chemoradiation on human pancreatic adenocarcinoma

Cytosine Deaminase-Uracil Phosphoribosyltransferase and Interleukin (IL)-12 and IL-18: A Multimodal Anticancer Interface Marked by Specific Modulation in Serum Cytokines

Leveraging the Activity of Tumor Vaccines with Cytotoxic Chemotherapy

Contact Info

Product

Resources

About

Treatment of colon and breast carcinoma cells with 5‐fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA‐A(*)02.01 restricted, CEA‐peptide‐specific cytotoxic T cells in vitro

Cited by 80 publications

References 33 publications

Synergistic effects of interferon-alpha in combination with chemoradiation on human pancreatic adenocarcinoma

Synergistic effects of interferon-alpha in combination with chemoradiation on human pancreatic adenocarcinoma

Cytosine Deaminase-Uracil Phosphoribosyltransferase and Interleukin (IL)-12 and IL-18: A Multimodal Anticancer Interface Marked by Specific Modulation in Serum Cytokines

Leveraging the Activity of Tumor Vaccines with Cytotoxic Chemotherapy

Contact Info

Product

Resources

About

Treatment of colon and breast carcinoma cells with 5‐fluorouracil enhances expression of carcinoembryonic antigen and susceptibility to HLA‐A()02.01 restricted, CEA‐peptide‐specific cytotoxic T cells in vitro*