PMID- 36223726 OWN - NLM STAT- MEDLINE VI - 55 IP - 10 TI - Spatial maps of T cell receptors and transcriptomes reveal distinct immune niches and interactions in the adaptive immune response. PG - 1940-1952.e5 CI - Copyright © 2022 Elsevier Inc. All rights reserved. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Immunity JT - Immunity JID - 9432918 IS - 1097-4180 (Electronic) LID - S1074-7613(22)00415-0 [pii] LID - 10.1016/j.immuni.2022.09.002 [doi] FAU - Liu, Sophia AU - Liu S AD - Biophysics Program, Harvard University, Boston, MA 02115, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. FAU - Iorgulescu, J Bryan AU - Iorgulescu JB AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. FAU - Li, Shuqiang AU - Li S AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA 02215, USA. FAU - Borji, Mehdi AU - Borji M AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. FAU - Barrera-Lopez, Irving A AU - Barrera-Lopez IA AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. FAU - Shanmugam, Vignesh AU - Shanmugam V AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. FAU - Lyu, Haoxiang AU - Lyu H AD - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA 02215, USA. FAU - Morriss, Julia W AU - Morriss JW AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. FAU - Garcia, Zoe N AU - Garcia ZN AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. FAU - Murray, Evan AU - Murray E AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. FAU - Reardon, David A AU - Reardon DA AD - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. FAU - Yoon, Charles H AU - Yoon CH AD - Department of Surgical Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. FAU - Braun, David A AU - Braun DA AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Yale Center of Cellular and Molecular Oncology, Yale School of Medicine, New Haven, CT 06511, USA. FAU - Livak, Kenneth J AU - Livak KJ AD - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA 02215, USA. FAU - Wu, Catherine J AU - Wu CJ AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Stem Cell Transplantation and Cellular Therapies, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: cwu@partners.org. FAU - Chen, Fei AU - Chen F AD - Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: chenf@broadinstitute.org. IS - 1074-7613 (Linking) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - Adaptive Immunity/genetics MH - Animals MH - Humans MH - Mice MH - *Receptors, Antigen, T-Cell MH - T-Lymphocytes MH - *Transcriptome OTO - NOTNLM OT - T cell OT - T cell receptor OT - cell interactions OT - clonotype OT - immune niches OT - sequencing OT - spatial OT - tertiary lymphoid structures OT - transcriptomics OT - tumor infiltrating lymphocytes PMC - PMC9745674 DCOM- 20221014 LR - 20240126 DP - 20221011 AB - T cells mediate antigen-specific immune responses to disease through the specificity and diversity of their clonotypic T cell receptors (TCRs). Determining the spatial distributions of T cell clonotypes in tissues is essential to understanding T cell behavior, but spatial sequencing methods remain unable to profile the TCR repertoire. Here, we developed Slide-TCR-seq, a 10-μm-resolution method, to sequence whole transcriptomes and TCRs within intact tissues. We confirmed the ability of Slide-TCR-seq to map the characteristic locations of T cells and their receptors in mouse spleen. In human lymphoid germinal centers, we identified spatially distinct TCR repertoires. Profiling T cells in renal cell carcinoma and melanoma specimens revealed heterogeneous immune responses: T cell states and infiltration differed intra- and inter-clonally, and adjacent tumor and immune cells exhibited distinct gene expression. Altogether, our method yields insights into the spatial relationships between clonality, neighboring cell types, and gene expression that drive T cell responses.