Concomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarization
Abstract Background The clinical observation showed a potential additive effect of anti-PD-1 agents and cetirizine in patients with advanced melanoma. Methods Clinical outcomes of concomitant cetirizine/anti-PD-1 treatment of patients with stage IIIb–IV melanoma were retrospectively collected, and a...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03643-w |
| _version_ | 1797817789360111616 |
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| author | Domenico Mallardo Ester Simeone Vito Vanella Maria Grazia Vitale Marco Palla Luigi Scarpato Miriam Paone Teresa De Cristofaro Valentina Borzillo Alessio Cortellini Francesca Sparano Sandro Pignata Francesco Fiore Corrado Caracò Piera Maiolino Antonella Petrillo Ernesta Cavalcanti Secondo Lastoria Paolo Muto Alfredo Budillon Sarah Warren Paolo Antonio Ascierto |
| author_facet | Domenico Mallardo Ester Simeone Vito Vanella Maria Grazia Vitale Marco Palla Luigi Scarpato Miriam Paone Teresa De Cristofaro Valentina Borzillo Alessio Cortellini Francesca Sparano Sandro Pignata Francesco Fiore Corrado Caracò Piera Maiolino Antonella Petrillo Ernesta Cavalcanti Secondo Lastoria Paolo Muto Alfredo Budillon Sarah Warren Paolo Antonio Ascierto |
| author_sort | Domenico Mallardo |
| collection | DOAJ |
| description | Abstract Background The clinical observation showed a potential additive effect of anti-PD-1 agents and cetirizine in patients with advanced melanoma. Methods Clinical outcomes of concomitant cetirizine/anti-PD-1 treatment of patients with stage IIIb–IV melanoma were retrospectively collected, and a transcriptomic analysis was performed on blood samples obtained at baseline and after 3 months of treatment. Results Patients treated with cetirizine concomitantly with an anti-PD-1 agent had significantly longer progression-free survival (PFS; mean PFS: 28 vs 15 months, HR 0.46, 95% CI: 0.28–0.76; p = 0.0023) and OS (mean OS was 36 vs 23 months, HR 0.48, 95% CI: 0.29–0.78; p = 0.0032) in comparison with those not receiving cetirizine. The concomitant treatment was significantly associated with ORR and DCR (p < 0.05). The expression of FCGR1A/CD64, a specific marker of macrophages, was increased after the treatment in comparison with baseline in blood samples from patients receiving cetirizine, but not in those receiving only the anti-PD1, and positively correlated with the expression of genes linked to the interferon pathway such as CCL8 (rho = 0.32; p = 0.0111), IFIT1 (rho = 0.29; p = 0.0229), IFIT3 (rho = 0.57; p < 0.0001), IFI27 (rho = 0.42; p = 0.008), MX1 (rho = 0.26; p = 0.0383) and RSAD2 (rho = 0.43; p = 0.0005). Conclusions This retrospective study suggests that M1 macrophage polarization may be induced by cetirizine through the interferon-gamma pathway. This effect may synergize with the immunotherapy of advanced melanoma with anti-PD-1 agents. |
| first_indexed | 2024-03-13T08:59:38Z |
| format | Article |
| id | doaj.art-a1de88eacd334c7ebe21732707f03220 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-13T08:59:38Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-a1de88eacd334c7ebe21732707f032202023-05-28T11:26:29ZengBMCJournal of Translational Medicine1479-58762022-09-0120111110.1186/s12967-022-03643-wConcomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarizationDomenico Mallardo0Ester Simeone1Vito Vanella2Maria Grazia Vitale3Marco Palla4Luigi Scarpato5Miriam Paone6Teresa De Cristofaro7Valentina Borzillo8Alessio Cortellini9Francesca Sparano10Sandro Pignata11Francesco Fiore12Corrado Caracò13Piera Maiolino14Antonella Petrillo15Ernesta Cavalcanti16Secondo Lastoria17Paolo Muto18Alfredo Budillon19Sarah Warren20Paolo Antonio Ascierto21Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Radiation Oncology Unit, Istituto Nazionale Tumori – IRCCS –Fondazione ”G. Pascale”Department of Surgery & Cancer, Imperial College London, Hammersmith HospitalMelanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Department of Urology and Gynecology, Istituto Nazionale Tumori – IRCCS –Fondazione ”G. Pascale”Interventional Radiology Unit, Istituto Nazionale Tumori – IRCCS –Fondazione ”G. Pascale”Division of Surgery of Melanoma and Skin Cancer, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Hospital Pharmacy, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Radiology Division, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Division of Laboratory Medicine, Istituto Nazionale Tumori – IRCCS –Fondazione ”G. Pascale”Nuclear Medicine Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Radiation Oncology Unit, Istituto Nazionale Tumori – IRCCS –Fondazione ”G. Pascale”Experimental Pharmacology Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”NanoString TechnologiesMelanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori – IRCCS – Fondazione ”G. Pascale”Abstract Background The clinical observation showed a potential additive effect of anti-PD-1 agents and cetirizine in patients with advanced melanoma. Methods Clinical outcomes of concomitant cetirizine/anti-PD-1 treatment of patients with stage IIIb–IV melanoma were retrospectively collected, and a transcriptomic analysis was performed on blood samples obtained at baseline and after 3 months of treatment. Results Patients treated with cetirizine concomitantly with an anti-PD-1 agent had significantly longer progression-free survival (PFS; mean PFS: 28 vs 15 months, HR 0.46, 95% CI: 0.28–0.76; p = 0.0023) and OS (mean OS was 36 vs 23 months, HR 0.48, 95% CI: 0.29–0.78; p = 0.0032) in comparison with those not receiving cetirizine. The concomitant treatment was significantly associated with ORR and DCR (p < 0.05). The expression of FCGR1A/CD64, a specific marker of macrophages, was increased after the treatment in comparison with baseline in blood samples from patients receiving cetirizine, but not in those receiving only the anti-PD1, and positively correlated with the expression of genes linked to the interferon pathway such as CCL8 (rho = 0.32; p = 0.0111), IFIT1 (rho = 0.29; p = 0.0229), IFIT3 (rho = 0.57; p < 0.0001), IFI27 (rho = 0.42; p = 0.008), MX1 (rho = 0.26; p = 0.0383) and RSAD2 (rho = 0.43; p = 0.0005). Conclusions This retrospective study suggests that M1 macrophage polarization may be induced by cetirizine through the interferon-gamma pathway. This effect may synergize with the immunotherapy of advanced melanoma with anti-PD-1 agents.https://doi.org/10.1186/s12967-022-03643-wMalignant melanomaAnti-PD-1CetirizineTumor-associated macrophageDrug repurposing |
| spellingShingle | Domenico Mallardo Ester Simeone Vito Vanella Maria Grazia Vitale Marco Palla Luigi Scarpato Miriam Paone Teresa De Cristofaro Valentina Borzillo Alessio Cortellini Francesca Sparano Sandro Pignata Francesco Fiore Corrado Caracò Piera Maiolino Antonella Petrillo Ernesta Cavalcanti Secondo Lastoria Paolo Muto Alfredo Budillon Sarah Warren Paolo Antonio Ascierto Concomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarization Journal of Translational Medicine Malignant melanoma Anti-PD-1 Cetirizine Tumor-associated macrophage Drug repurposing |
| title | Concomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarization |
| title_full | Concomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarization |
| title_fullStr | Concomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarization |
| title_full_unstemmed | Concomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarization |
| title_short | Concomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarization |
| title_sort | concomitant medication of cetirizine in advanced melanoma could enhance anti pd 1 efficacy by promoting m1 macrophages polarization |
| topic | Malignant melanoma Anti-PD-1 Cetirizine Tumor-associated macrophage Drug repurposing |
| url | https://doi.org/10.1186/s12967-022-03643-w |
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