Pan-cancer spatial atlas of tertiary lymphoid structures
(1) Cho KS (2) Liu Y (3) Pei G (4) Chen J (5) Dai Y (6) Liu Y (7) Zhou T (8) Bougouin A (9) Serrano A (10) Wani K (11) Jadhav A (12) Min J (13) Hernandez S (14) Lu W (15) Zhang D (16) Jiang J (17) Shamsutdinova D (18) Dai E (19) Peng F (20) Sinjab A (21) Guerrero PA (22) Julio ICL (23) Yu K (24) Clark H (25) Maru D (26) Li M (27) Futreal A (28) Lee S (29) Solis Soto LM (30) Shang L (31) Msaouel P (32) Ajani JA (33) Beird H (34) Jazaeri AA (35) Lazar AJ (36) Sautes-Fridman C (37) Fridman WH (38) Maitra A (39) Kadara H (40) Gao J (41) Sharma P (42) Wang L
Cho et al. integrated whole-section (WS) spatial transcriptomics across 12 cancer types to construct a pan-cancer tertiary lymphoid structure (TLS) atlas. TLSs spanned early, primary, and secondary maturation states with distinct spatial niches and immune organization. Tumor regions proximal to intratumoral TLSs showed enriched antigen-presentation and IFN-response programs, and reduced proliferative and EMT signatures. An AI framework trained on whole-slide H&E images classified TLS maturation and maturation-aware TLS composite scores, which stratified survival and treatment response, outperforming conventional TLS metrics.
Contributed by Shishir Pant
(1) Cho KS (2) Liu Y (3) Pei G (4) Chen J (5) Dai Y (6) Liu Y (7) Zhou T (8) Bougouin A (9) Serrano A (10) Wani K (11) Jadhav A (12) Min J (13) Hernandez S (14) Lu W (15) Zhang D (16) Jiang J (17) Shamsutdinova D (18) Dai E (19) Peng F (20) Sinjab A (21) Guerrero PA (22) Julio ICL (23) Yu K (24) Clark H (25) Maru D (26) Li M (27) Futreal A (28) Lee S (29) Solis Soto LM (30) Shang L (31) Msaouel P (32) Ajani JA (33) Beird H (34) Jazaeri AA (35) Lazar AJ (36) Sautes-Fridman C (37) Fridman WH (38) Maitra A (39) Kadara H (40) Gao J (41) Sharma P (42) Wang L
Cho et al. integrated whole-section (WS) spatial transcriptomics across 12 cancer types to construct a pan-cancer tertiary lymphoid structure (TLS) atlas. TLSs spanned early, primary, and secondary maturation states with distinct spatial niches and immune organization. Tumor regions proximal to intratumoral TLSs showed enriched antigen-presentation and IFN-response programs, and reduced proliferative and EMT signatures. An AI framework trained on whole-slide H&E images classified TLS maturation and maturation-aware TLS composite scores, which stratified survival and treatment response, outperforming conventional TLS metrics.
Contributed by Shishir Pant
ABSTRACT: Tertiary lymphoid structures (TLSs) are critical regulators of antitumor immunity, yet their spatial organization, maturation, and clinical relevance remain incompletely defined across cancers. We analyzed spatial transcriptomics spanning 12 cancer types to construct a pan-cancer TLS atlas and characterized TLS spatial architecture and maturation states. TLS maturation was accompanied by coordinated remodeling of distinct niche cell populations and distance-dependent gradients in tumor programs, orthogonally supported by ultrahigh-plex single-cell spatial profiling. To enable scalable TLS profiling, we trained an artificial intelligence framework that predicts TLS maturation states directly from hematoxylin and eosin-stained images and evaluated it across TCGA and independent therapy cohorts. We further derived a maturation-aware composite score capturing intratumoral TLS state composition, which robustly stratifies patients across cancer and treatment contexts, outperforming conventional TLS metrics.
Author Info:
(1) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (2) Department of Genomic Medicine, The University of Texas MD Anderson Can
cer Center, Houston, TX, USA. (3) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (4) Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (5) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences; Houston, TX, USA. (6) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (7) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (8) Centre de Recherche des Cordeliers, Sorbonne Universit, INSERM, Universite Paris Cite, Equipe labellise Ligue Contre le Cancer, Paris, France. (9) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (10) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (11) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (12) Laura and Isaac Perlmutter Cancer Center, Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA. (13) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (14) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (15) Department of Biostatistics, The University of North Carolina, Chapel Hill, NC, USA. Department of Genetics, The University of North Carolina, Chapel Hill, NC, USA. (16) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (17) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (18) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (19) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (20) Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (21) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (22) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (23) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (24) Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (25) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (26) Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. (27) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (28) Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (29) Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (30) Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (31) Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences; Houston, TX, USA. (32) Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (33) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (34) Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (35) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences; Houston, TX, USA. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (36) Centre de Recherche des Cordeliers, Sorbonne Universit, INSERM, Universite Paris Cite, Equipe labellise Ligue Contre le Cancer, Paris, France. (37) Centre de Recherche des Cordeliers, Sorbonne Universit, INSERM, Universite Paris Cite, Equipe labellise Ligue Contre le Cancer, Paris, France. (38) Laura and Isaac Perlmutter Cancer Center, Department of Medicine, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA. Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA. (39) The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences; Houston, TX, USA. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center; Houston, TX, USA. (40) Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (41) Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (42) Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences; Houston, TX, USA. James P. Allison Institute, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Institute for Data Science in Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Center for Cellular Language Intelligence, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Citation: Science 2026 May 28 392:eadz2742 Epub05/28/2026
