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Cancer Immunology Miniatures

Pulmonary Sarcoid–like Granulomatosis after Multiple Vaccinations of a Long-term Surviving Patient with Metastatic Melanoma

Natacha Bordry, Carla-Marisa Costa-Nunes, Laurène Cagnon, Philippe O. Gannon, Samia Abed-Maillard, Petra Baumgaertner, Timothy Murray, Igor Letovanec, Romain Lazor, Hasna Bouchaab, Nathalie Rufer, Emanuela Romano, Olivier Michielin and Daniel E. Speiser
Natacha Bordry
1Clinical and Tumor Biology and Immunotherapy Unit, Department of Oncology and Ludwig Cancer Research Center, University of Lausanne (UNIL), Lausanne, Switzerland.
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Carla-Marisa Costa-Nunes
1Clinical and Tumor Biology and Immunotherapy Unit, Department of Oncology and Ludwig Cancer Research Center, University of Lausanne (UNIL), Lausanne, Switzerland.
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Laurène Cagnon
1Clinical and Tumor Biology and Immunotherapy Unit, Department of Oncology and Ludwig Cancer Research Center, University of Lausanne (UNIL), Lausanne, Switzerland.
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Philippe O. Gannon
1Clinical and Tumor Biology and Immunotherapy Unit, Department of Oncology and Ludwig Cancer Research Center, University of Lausanne (UNIL), Lausanne, Switzerland.
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Samia Abed-Maillard
1Clinical and Tumor Biology and Immunotherapy Unit, Department of Oncology and Ludwig Cancer Research Center, University of Lausanne (UNIL), Lausanne, Switzerland.
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Petra Baumgaertner
1Clinical and Tumor Biology and Immunotherapy Unit, Department of Oncology and Ludwig Cancer Research Center, University of Lausanne (UNIL), Lausanne, Switzerland.
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Timothy Murray
1Clinical and Tumor Biology and Immunotherapy Unit, Department of Oncology and Ludwig Cancer Research Center, University of Lausanne (UNIL), Lausanne, Switzerland.
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Igor Letovanec
2Department of Pathology, Lausanne University Hospital Center (CHUV), Lausanne, Switzerland.
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Romain Lazor
3Department of Respiratory Medicine, CHUV, Lausanne, Switzerland.
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Hasna Bouchaab
4Department of Oncology, CHUV and UNIL, Lausanne, Switzerland.
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Nathalie Rufer
1Clinical and Tumor Biology and Immunotherapy Unit, Department of Oncology and Ludwig Cancer Research Center, University of Lausanne (UNIL), Lausanne, Switzerland.
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Emanuela Romano
4Department of Oncology, CHUV and UNIL, Lausanne, Switzerland.
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Olivier Michielin
4Department of Oncology, CHUV and UNIL, Lausanne, Switzerland.
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Daniel E. Speiser
1Clinical and Tumor Biology and Immunotherapy Unit, Department of Oncology and Ludwig Cancer Research Center, University of Lausanne (UNIL), Lausanne, Switzerland.
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  • For correspondence: doc@dspeiser.ch
DOI: 10.1158/2326-6066.CIR-14-0143 Published December 2014
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    Figure 1.

    Radiologic images and disease course. A to E, cerebral MRI. White circles, brain metastasis. F to N, thoracic CT scan. Red circles, right paratracheal lymphadenopathies (I and L), right (J and M), and left hilar lymphadenopathies (K and N). F, G, and H, no lymphadenopathies. O to P, whole body PET-CT scan. Black arrows, left axillary lymphadenopathy and left anterior chest wall nodule. Bottom, timeline showing therapy and disease status. Sentinel lymph node procedure (Sent. LN). Lymph node metastasis surgery 1 (LN1), right iliac obdurator and inguinal radical lymph node dissection. LN2, right and left pelvic lymph node dissection. LN3, left axillary lymph node dissection + mediastinoscopy + left anterior chest wall nodule resection. Subcutaneous melanoma metastasis resection 1 (Subcut. MM1), right parapubic subcutaneous nodule resection. Subcut. MM2, right subpubic subcutaneous nodule resection. Subcut. MM3, right inguinal subcutaneous nodule resection. Sarcoid-like granulomatosis (Sarc-.LG). SB-AS2: i.d. vaccines 1, 3, and 5 of Melan-A + MAGE-A10; i.m. vaccines 2, 4 and 6 of Melan-A + MAGE-A10 + SB-AS2. ISA-51: s.c vaccines of Melan-A + MAGE-A10 + NY-ESO-1 + Montanide. ISA-51 + CpG, s.c. vaccines of Melan-A + MAGE-A10 + NY-ESO-1 + Montanide+ CpG. CpG, s.c. vaccines of Melan-A + MAGE-A10 + NY-ESO-1 + CpG; MM, melanoma metastasis; NED, no evidence of disease. PD, progressive disease; vertical arrows, surgeries; irradiation symbol + vertical arrow, radiosurgery.

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    Figure 2.

    Immunohistochemical analysis of immune cells in paraffin-embedded right paratracheal lymph nodes. A, CD68+ macrophages. B, CD4+ T lymphocytes. C, CD8+ T lymphocytes. D, CD45RO+ lymphocytes. E, FoxP3+ lymphocytes. F, CD25+ lymphocytes. All images were taken from the same tissue section. IHC with isotype control antibodies were negative (not shown).

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    Figure 3.

    T-cell responses. A, representative example dot plots from PBMCs, showing Melan-A–specific cells (left), of NY-ESO-1–specific cells (middle), and MAGE-A10–specific cells (right) among CD8+ T cells. B, percentages of CD3+, CD4+, and CD8+ T cells in PBMCs. C, direct ex vivo ELISPOT analysis of total PBMCs, IFNγ production after 24 hours incubation with specific peptides (Melan-A, NY-ESO-1, and MAGE-A10). Ex vivo tetramer analysis of Melan-A– (D), NY-ESO-1– (F), and MAGE-A10 (H)–specific CD8+ T cells after the different vaccinations. Percentages of CD28− cells among the Melan-A–specific (E), NY-ESO-1–specific (G), and MAGE-A10–specific (I) CD8+ T cells.

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Cancer Immunology Research: 2 (12)
December 2014
Volume 2, Issue 12
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Pulmonary Sarcoid–like Granulomatosis after Multiple Vaccinations of a Long-term Surviving Patient with Metastatic Melanoma
Natacha Bordry, Carla-Marisa Costa-Nunes, Laurène Cagnon, Philippe O. Gannon, Samia Abed-Maillard, Petra Baumgaertner, Timothy Murray, Igor Letovanec, Romain Lazor, Hasna Bouchaab, Nathalie Rufer, Emanuela Romano, Olivier Michielin and Daniel E. Speiser
Cancer Immunol Res December 1 2014 (2) (12) 1148-1153; DOI: 10.1158/2326-6066.CIR-14-0143

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Pulmonary Sarcoid–like Granulomatosis after Multiple Vaccinations of a Long-term Surviving Patient with Metastatic Melanoma
Natacha Bordry, Carla-Marisa Costa-Nunes, Laurène Cagnon, Philippe O. Gannon, Samia Abed-Maillard, Petra Baumgaertner, Timothy Murray, Igor Letovanec, Romain Lazor, Hasna Bouchaab, Nathalie Rufer, Emanuela Romano, Olivier Michielin and Daniel E. Speiser
Cancer Immunol Res December 1 2014 (2) (12) 1148-1153; DOI: 10.1158/2326-6066.CIR-14-0143
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