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

被引：14

作者：

Lee, Hansol ^{[1
,2
,3
]}

Ferguson, Angela L. ^{[2
,3
,4
,5
]}

Quek, Camelia ^{[1
,2
,3
]}

Vergara, Ismael A. ^{[1
,2
,3
]}

daSilva, Ines Pires ^{[1
,2
,3
,6
]}

Allen, Ruth ^{[2
,3
]}

Gide, Tuba Nur ^{[1
,2
,3
]}

Conway, Jordan W. ^{[1
,2
,3
]}

Koufariotis, Lambros T. ^{[7
]}

Hayward, Nicholas K. ^{[7
]}

Waddell, Nicola ^{[7
]}

Carlino, Matteo S. ^{[1
,8
]}

Menzies, Alexander M. ^{[1
,2
,8
,9
]}

Saw, Robyn P. M. ^{[1
,2
,9
,10
]}

Shklovskaya, Elena ^{[1
,11
]}

Rizos, Helen ^{[1
,11
]}

Lo, Serigne ^{[1
,2
]}

Scolyer, Richard A. ^{[1
,2
,3
,10
,12
]}

V. Long, Georgina ^{[1
,2
,3
,8
,9
]}

Palendira, Umaimaintha ^{[1
,2
,3
,4
,5
]}

Wilmott, James S. ^{[1
,2
,3
,13
]}

机构：

[1] Univ Sydney, Melanoma Inst Australia, Sydney, NSW, Australia

[2] Univ Sydney, Fac Med & Hlth, Sydney, NSW, Australia

[3] Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia

[4] Univ Sydney, Centenary Inst, Sydney, NSW, Australia

[5] Univ Sydney, Charles Perkins Ctr, Sch Med Sci, Infect Immun & Inflammat Theme, Sydney, NSW, Australia

[6] Westmead & Blacktown Hosp, Sydney, NSW, Australia

[7] QIMR Berghofer Med Res Inst, Herston, Qld, Australia

[8] Royal North Shore Hosp, Sydney, NSW, Australia

[9] Mater Hosp, North Sydney, NSW, Australia

[10] Royal Prince Alfred Hosp, Sydney, NSW, Australia

[11] Macquarie Univ, Fac Med Hlth & Human Sci, Sydney, NSW, Australia

[12] NSW Hlth Pathol, Sydney, NSW, Australia

[13] Univ Sydney, Charles Perkins Ctr, Cent Clin Sch, Sydney, NSW 2037, Australia

来源：

CLINICAL CANCER RESEARCH | 2023年 / 29卷 / 13期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

TUMOR-ASSOCIATED MACROPHAGES; CELL-MEDIATED CYTOTOXICITY; MONOCLONAL-ANTIBODY; T-CELLS; DEPENDENT CYTOTOXICITY; B-CELLS; RITUXIMAB; COMPLEMENT; EXPRESSION; CD16;

D O I：

10.1158/1078-0432.CCR-22-2657

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: This study characterizes intratumoral macrophage populations within baseline melanoma biopsies from patients with advanced melanoma who received either anti-PD-1 mono-therapy or a combination with anti-CTLA-4. Particularly, FcyRIIIa (CD16)-expressing macrophage densities were inves-tigated 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 & PLUSMN; macrophage densities than those who did not respond (196 vs. 7 cells/mm2; P = 0.0041). There was no diffidence in CD16 & PLUSMN; 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 & PLUSMN; 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 & PLUSMN; macrophages contained upregulated gene expression of critical T-cell recruiting chemokines (CXCL9, CXCL10, and CXCL11). Conclusions: Our data demonstrate that tumor microenviron-ments enriched with CD16 & PLUSMN; 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

引用

页码：2513 / 2524

页数：12

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