期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-26974-6
关键词
-
资金
- National Institutes of Health (NIH) [R33CA183692, R01HL128173-04, 5P01AI131374-02, 5UG3DK114937-02, 1U19AI135976-01, IDIQ17X149, 1U2CCA233238-01, 1U2CCA233195-01, F32CA233203, T32AR007422, T32AI007290]
- National Cancer Institute [U01CA154967, UM1CA154967]
- Cancer Center Support Grant [P30 CA015704]
- Department of Defense [W81XWH-14-1-0180, W81XWH-12-1-0591]
- Food and Drug Administration [HHSF223201610018C, DSTL/AGR/00980/01]
- Cancer Research UK [C27165/A29073]
- Bill and Melinda Gates Foundation [OPP1113682]
- Cancer Research Institute
- Parker Institute for Cancer Immunotherapy
- Kenneth Rainin Foundation
- Celgene, Inc. [133826, 134073]
- Rachford & Carlotta A. Harris Endowed Chair
- Beckman Center for Molecular and Genetic Medicine
- Stanford Dean's Fellowship
- Stanford Cancer Institute Fellowship
- Swiss National Science Foundation [P300PB_171189, P400PM_183915]
- International Award for Research in Leukemia from the Lady Tata Memorial Trust, London, UK
- Bio-X Stanford Interdisciplinary Graduate Fellowship
- Stanford Bioengineering
- Leukemia & Lymphoma Society Career Development Program
- The National Institutes of Health (NIH) [2U19AI057229-16, 5P01HL10879707, 5R01GM10983604, 5R33CA18365403, 5U01AI101984-07, 5UH2AR06767604, 5R01CA19665703, 5U54CA20997103, 5F99CA212231-02, 1F32CA233203-01, 5U01AI140498-02, 1U54HG010426-01, 5U19AI100627-07, 1R01HL120724-01A1]
- Swiss National Science Foundation (SNF) [P300PB_171189, P400PM_183915] Funding Source: Swiss National Science Foundation (SNF)
This study reveals a spatial biomarker that utilizes immune and cancer cell topography to predict response to PD-1 blockade in cutaneous T cell lymphomas. The biomarker is strongly correlated with the functional immune state of the tumor microenvironment, T cell function, and tumor cell-specific chemokine recruitment.
Cutaneous T cell lymphomas (CTCL) are rare but aggressive cancers without effective treatments. While a subset of patients derive benefit from PD-1 blockade, there is a critically unmet need for predictive biomarkers of response. Herein, we perform CODEX multiplexed tissue imaging and RNA sequencing on 70 tumor regions from 14 advanced CTCL patients enrolled in a pembrolizumab clinical trial (NCT02243579). We find no differences in the frequencies of immune or tumor cells between responders and non-responders. Instead, we identify topographical differences between effector PD-1(+) CD4(+) T cells, tumor cells, and immunosuppressive Tregs, from which we derive a spatial biomarker, termed the SpatialScore, that correlates strongly with pembrolizumab response in CTCL. The SpatialScore coincides with differences in the functional immune state of the tumor microenvironment, T cell function, and tumor cell-specific chemokine recruitment and is validated using a simplified, clinically accessible tissue imaging platform. Collectively, these results provide a paradigm for investigating the spatial balance of effector and suppressive T cell activity and broadly leveraging this biomarker approach to inform the clinical use of immunotherapies. PD-1 blockade is effective for only a subset of patients with cutaneous T cell lymphomas. Here, the authors report a spatial biomarker that uses immune and cancer cell topography to predict response to PD-1 blockade in this disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据