Intratumoral CD16+ Macrophages Are Associated with Clinical Outcomes of Patients with Metastatic Melanoma Treated with Combination Anti-PD-1 and Anti-CTLA-4 Therapy-Reference-Cited by-同舟云学术

Intratumoral CD16+ Macrophages Are Associated with Clinical Outcomes of Patients with Metastatic Melanoma Treated with Combination Anti-PD-1 and Anti-CTLA-4 Therapy

Published:2023-02-15 Issue:13 Volume:29 Page:2513-2524
ISSN:1078-0432
Container-title:Clinical Cancer Research
language:en
Short-container-title:

Author:

Lee Hansol¹²³^ORCID,Ferguson Angela L.²³⁴⁵^ORCID,Quek Camelia¹²³^ORCID,Vergara Ismael A.¹²³^ORCID,Pires daSilva Ines¹²³⁶^ORCID,Allen Ruth²³^ORCID,Gide Tuba Nur¹²³^ORCID,Conway Jordan W.¹²³^ORCID,Koufariotis Lambros T.⁷^ORCID,Hayward Nicholas K.⁷^ORCID,Waddell Nicola⁷^ORCID,Carlino Matteo S.¹⁸^ORCID,Menzies Alexander M.¹²⁸⁹^ORCID,Saw Robyn P.M.¹²⁹¹⁰^ORCID,Shklovskaya Elena¹¹¹^ORCID,Rizos Helen¹¹¹^ORCID,Lo Serigne¹²^ORCID,Scolyer Richard A.¹²³¹⁰¹²^ORCID,Long Georgina V.¹²³⁸⁹^ORCID,Palendira Umaimainthan¹²³⁴⁵^ORCID,Wilmott James S.¹²³^ORCID

Affiliation:

1. 1Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.

2. 2Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

3. 3Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

4. 4Centenary Institute, The University of Sydney, Sydney, New South Wales, Australia.

5. 5Infection, Immunity and Inflammation theme, School of Medical Sciences, The Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

6. 6Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia.

7. 7QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.

8. 8Royal North Shore Hospital, Sydney, New South Wales, Australia.

9. 9Mater Hospital, North Sydney, New South Wales, Australia.

10. 10Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.

11. 11Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.

12. 12NSW Health Pathology, Sydney, New South Wales, Australia.

Abstract

Abstract Purpose: This study characterizes intratumoral macrophage populations within baseline melanoma biopsies from patients with advanced melanoma who received either anti-PD-1 monotherapy or a combination with anti-CTLA-4. Particularly, FcγRIIIa (CD16)-expressing macrophage densities were investigated for associations with response and progression-free survival. Experimental Design: Patients with advanced melanoma who received either anti-PD-1 monotherapy or combination anti-PD-1 and anti-CTLA-4 were retrospectively identified. Macrophage populations were analyzed within baseline melanoma biopsies via multiplex IHC in relation to treatment outcomes. Results: Patients who responded to combination immune checkpoint inhibitor contained higher CD16+ macrophage densities than those who did not respond (196 vs. 7 cells/mm2; P = 0.0041). There was no diffidence in CD16+ macrophage densities in the PD-1 monotherapy-treated patients based on response (118 vs. 89 cells/mm2; P = 0.29). A significantly longer 3-year progression-free survival was observed in combination-treated patients with high intratumoral densities of CD16+ macrophages compared with those with low densities (87% vs. 42%, P = 0.0056, n = 40). No association was observed in anti-PD-1 monotherapy-treated patients (50% vs. 47%, P = 0.4636, n = 50). Melanoma biopsies with high densities of CD16+ macrophages contained upregulated gene expression of critical T-cell recruiting chemokines (CXCL9, CXCL10, and CXCL11). Conclusions: Our data demonstrate that tumor microenvironments enriched with CD16+ macrophages are favorable for response to combination anti-PD-1 and anti-CTLA-4 therapy but not anti-PD-1 monotherapy. These data provides a potential biomarker of response for combination immunotherapies in patients with metastatic melanoma. See related commentary by Smithy and Luke, p. 2345

Funder

National Health and Medical Research Council

Melanoma Research Alliance

Cancer Institute NSW

Apex Foundation

Cancer Council NSW

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

Link

https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-22-2657/3270066/ccr-22-2657.pdf