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K. Suzawa
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-036 - Primary Pulmonary Melanoma: A Report of Two Cases (ID 2109)
09:30 - 09:30 | Author(s): K. Suzawa
- Abstract
Background:
Malignant melanoma is a refractory malignancy with a dismal prognosis. It generally arises from the skin in most cases, and cases of primary pulmonary malignant melanoma are rare and often behave aggressively. We have treated two cases of localized primary pulmonary malignant melanoma by surgical resection. Although cutaneous melanomas often carry activating mutations in the BRAF gene (V600E) and express programmed death ligand 1 (PD-L1), little is known about primary pulmonary malignant melanoma.
Methods:
We determined the BRAF mutational status (exons 11 and 15) by direct sequencing in the two tumors. Next, we performed a target sequencing analysis using the Human Lung Cancer Panel (Qiagen, Hilden, Germany), which targets 20 lung cancer-related genes including most of the exons in BRAF, using the same samples. We evaluated the expression of PD-L1 on the surface of the tumor cells by immunohistochemical testing in formalin-fixed, paraffin-embedded tumor specimens with the use of a rabbit monoclonal antihuman PD-L1 antibody.
Results:
No BRAF mutations and PD-L1 expression were detected in both of two cases. We detected a p53 mutation, which was thought to be a potential somatic mutation, in one of the two cases using a sequencing panel targeting 20 lung cancer-related genes.
Conclusion:
We encountered two cases of malignant melanoma of the lung that did not carry activating mutations in the BRAF gene. Further molecular analyses may uncover the characteristics of primary malignant melanoma.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-065 - Distant Bystander Effect of REIC/Dkk-3 Gene Therapy through Immune System Stimulation in a Murine Model of Thoracic Malignancies (ID 3006)
09:30 - 09:30 | Author(s): K. Suzawa
- Abstract
Background:
We previously identified the tumor suppressor gene REIC/Dkk-3 whose expression is reduced in many human cancers, and overexpression of REIC/Dkk-3 by an adenovirus (Ad-REIC) exhibited a dramatic therapeutic effect on several human cancers through a mechanism triggered by endoplasmic reticulum (ER) stress. In addition to the direct anti-tumor effect, we also have shown that Ad-REIC has a host-mediated bystander effect on human prostate cancer and scirrhous gastric cancer through REIC-mediated cancer vaccination and production of IL-7. In this study, we examined possible direct and indirect distant bystander effects of Ad-REIC via activation of systemic anti-tumor immunity on thoracic malignancies.
Methods:
We examined anti-tumor effect of Ad-REIC gene therapy on lung cancer and malignant mesothelioma (MM) cell lines in vitro. In addition, we examined the direct and distant bystander effect of Ad-REIC in bilateral flank allograft tumor model using immunocompetent BALB/c mice. Mice received intratumoral injection of Ad-REIC into the right-flank tumors, and the effect in bilateral-flank tumors were examined. Dissected bilateral flank tumors after sacrifice were also subjected to immunohistochemical analysis.
Results:
Ad-REIC treatment showed anti-tumor effect in many of lung cancer and MM cell lines in vitro due to the activation of c-Jun N-terminal kinase (JNK). REIC/Dkk-3 was highly expressed after Ad-SGE-REIC treatment in Ad-SGE-REIC sensitive cell lines, while it was not or weakly expressed in some cells, which were resist to Ad-SGE-REIC treatment. In an in vivo model, Ad-REIC treatment inhibited the tumorigenic growth of not only direct injected tumor but also distant non-injected tumor. In immunohistochemical examination, infiltration of CD49b positive NK cells and expression of MHC Class-I molecules H60 and Rae-1 were revealed in bilateral tumors, suggesting that Ad-REIC treatment showed bystander anti-tumor effect through immune system-mediated apoptosis, and protein expression of MHC class-I molecules induces NK cell infiltration to the tumor.
Conclusion:
We newly revealed that Ad-REIC treatment induced MHC Class-I expression both in primary and distant tumor sites, which lead NK cell infiltration. Ad-REIC treatment showed not only direct anti-tumor effect but also indirect bystander effect through immune system stimulation in immunocompetent mice model.　Our findings suggest that Ad-REIC therapy is a promising treatment for MM and lung cancer
