1. T cell-mediated curation and restructuring of tumor tissue coordinates an effective immune response.
- Author
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Hickey JW, Haist M, Horowitz N, Caraccio C, Tan Y, Rech AJ, Baertsch MA, Rovira-Clavé X, Zhu B, Vazquez G, Barlow G, Agmon E, Goltsev Y, Sunwoo JB, Covert M, and Nolan GP
- Subjects
- Humans, CD8-Positive T-Lymphocytes, Immunotherapy methods, Cytokines, Immunity, Tumor Microenvironment, Melanoma pathology
- Abstract
Antigen-specific T cells traffic to, are influenced by, and create unique cellular microenvironments. Here we characterize these microenvironments over time with multiplexed imaging in a melanoma model of adoptive T cell therapy and human patients with melanoma treated with checkpoint inhibitor therapy. Multicellular neighborhood analysis reveals dynamic immune cell infiltration and inflamed tumor cell neighborhoods associated with CD8
+ T cells. T cell-focused analysis indicates T cells are found along a continuum of neighborhoods that reflect the progressive steps coordinating the anti-tumor immune response. More effective anti-tumor immune responses are characterized by inflamed tumor-T cell neighborhoods, flanked by dense immune infiltration neighborhoods. Conversely, ineffective T cell therapies express anti-inflammatory cytokines, resulting in regulatory neighborhoods, spatially disrupting productive T cell-immune and -tumor interactions. Our study provides in situ mechanistic insights into temporal tumor microenvironment changes, cell interactions critical for response, and spatial correlates of immunotherapy outcomes, informing cellular therapy evaluation and engineering., Competing Interests: Declaration of interests G.P.N. has equity in and is a scientific advisory board member of Akoya Biosciences, Inc. A.J.R. is an advisor for Affini-T Therapeutics. G.P.N. and J.W.H. share a patent related to this work. The other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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