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| Status |
Public on Mar 01, 2017 |
| Title |
Immunologic Effects of a Peptide Vaccine with Intralesional IFNgamma For Treatment of Melanoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Introduction: Optimal approaches to induce T-cell infiltration of tumors are not known. Chemokines CXCL9, CXCL10, and CXCL11 support effector T-cell recruitment, and may be induced by IFNgamma. This study tests the hypothesis that intratumoral administration of IFNgamma will induce CXCL9-11, and will induce T-cell recruitment and anti-tumor immune signatures in melanoma metastases. Patients and Methods: Nine eligible patients were immunized with a vaccine comprised of 12 class I MHC-restricted melanoma peptides (12MP) and received IFNgamma intratumorally. Effects on the tumor microenvironment (TME) were evaluated in sequential tumor biopsies. Adverse events (AE; CTCAE v4) were recorded. T-cell responses to vaccination were assessed in peripheral blood (PBMC) by IFNgamma ELIspot assay. Tumor biopsies were evaluated for immune cell infiltration, chemokine protein expression and gene expression. Results: Vaccination and intratumoral administration of IFNgamma were well tolerated. Circulating T-cell responses to vaccine were detected in 6 of 9 patients. IFNgamma increased production of chemokines CXCL10, CXCL11, and CCL5 in patient tumors. Neither vaccination alone nor the addition of IFNgamma promoted immune cell infiltration or induced anti-tumor immune gene signatures. Conclusion: The cancer vaccine did not significantly increase T-cell infiltration of tumors. This study provides intriguing findings highlighting some of the limitations of intratumoral IFNgamma treatment. Although IFNgamma is pivotal in anti-tumor immunity, single intratumoral injection may induce secondary immune regulation that paradoxically limits immune infiltration and effector functions. Therefore, alternate dosing strategies or additional combinatorial treatments may be needed to optimally promote trafficking and retention of T-cells in tumor, which merit further study.
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| Overall design |
Biopsies (incisional, core or excisional biopsies) of cutaneous or subcutaneous metastatic melanoma were obtained on day 1 (baseline, pre-treatment) (n=7), day 22 (1 week after the third vaccine) (n=7) and day 24 (48 hrs after intratumoral injection of IFNgamma (n=7). When possible, biopsies at day 24 included both a tumor injected with IFNgamma (n=7) and one uninjected (n=3).
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| Citation missing |
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| Submission date |
Mar 30, 2016 |
| Last update date |
Mar 15, 2019 |
| Contact name |
Francesco Maria Marincola |
| E-mail(s) |
fmarincola@sidra.org
|
| Phone |
301-793-8210
|
| Organization name |
Sidra Medical and Research Center
|
| Street address |
Al Nasr Tower, AL Corniche Street, PO Box 26999
|
| City |
Doha |
| ZIP/Postal code |
PO Box 26999 |
| Country |
Qatar |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (24)
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| GSM2101877 |
Patient 1 - Pre-treatment Biopsy - Day 1 - mAdbID:125508 |
| GSM2101878 |
Patient 1 - Biopsy with IFNgamma - Day 22 - mAdbID:125509 |
| GSM2101879 |
Patient 1 - Biopsy with IFNgamma - Day 24 - mAdbID:125510 |
| GSM2101880 |
Patient 3 - Pre-treatment Biopsy - Day 1 - mAdbID:125511 |
| GSM2101881 |
Patient 3 - Biopsy with IFNgamma - Day 22 - mAdbID:125512 |
| GSM2101882 |
Patient 3 - Biopsy with IFNgamma - Day 24 - mAdbID:125513 |
| GSM2101883 |
Patient 4 - Pre-treatment Biopsy - Day 1 - mAdbID:125514 |
| GSM2101884 |
Patient 4 - Biopsy with IFNgamma - Day 22 - mAdbID:125515 |
| GSM2101885 |
Patient 4 - Biopsy with IFNgamma - Day 24 - mAdbID:125516 |
| GSM2101886 |
Patient 4 - Untreated Biopsy - Day 24 - mAdbID:125517 |
| GSM2101887 |
Patient 5 - Pre-treatment Biopsy - Day 1 - mAdbID:125518 |
| GSM2101888 |
Patient 5 - Biopsy with IFNgamma - Day 22 - mAdbID:125519 |
| GSM2101889 |
Patient 5 - Biopsy with IFNgamma - Day 24 - mAdbID:125520 |
| GSM2101890 |
Patient 6 - Pre-treatment Biopsy - Day 1 - mAdbID:125521 |
| GSM2101891 |
Patient 6 - Biopsy with IFNgamma - Day 22 - mAdbID:125522 |
| GSM2101892 |
Patient 6 - Untreated Biopsy - Day 24 - mAdbID:125523 |
| GSM2101893 |
Patient 6 - Biopsy with IFNgamma - Day 24 - mAdbID:125524 |
| GSM2101894 |
Patient 7 - Pre-treatment Biopsy - Day 1 - mAdbID:125525 |
| GSM2101895 |
Patient 7 - Biopsy with IFNgamma - Day 22 - mAdbID:125526 |
| GSM2101896 |
Patient 7 - Biopsy with IFNgamma - Day 24 - mAdbID:125527 |
| GSM2101897 |
Patient 8 - Pre-treatment Biopsy - Day 1 - mAdbID:125528 |
| GSM2101898 |
Patient 8 - Biopsy with IFNgamma - Day 22 - mAdbID:125529 |
| GSM2101899 |
Patient 8 - Untreated Biopsy - Day 24 - mAdbID:125530 |
| GSM2101900 |
Patient 8 - Biopsy with IFNgamma - Day 24 - mAdbID:125531 |
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| Relations |
| BioProject |
PRJNA316868 |
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