Tertiary lymphoid structures improve immunotherapy and survival in melanoma
Abstract
Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers 1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota 2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Tumor-associated tertiary lymphoid structures are emerging as a powerful prognostic marker in melanoma and a number of other cancer types.
“Also, as a member of the 12-chemokine gene signature classifier33, its expression has been correlated with the presence of tumor-associated tertiary lymphoid structures50–52 which are rapidly emerging as a powerful prognostic marker in melanoma and a number of other cancer types53–55.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [53]
The findings were corroborated in translational studies of separate melanoma and sarcoma cohorts treated with ICB.
“Moreover, these findings were corroborated in translational studies of separate cohorts of patients with melanoma36 and sarcoma37 who were treated with ICB.”
From B cells and tertiary lymphoid structures promote immunotherapy response (2020) · cites this paper as [36]
Presence of B cells in tumor is associated with better response to neoadjuvant ICB in melanoma and renal cell carcinoma.
“Presence of B cells in tumor was associated with a better response to neoadjuvant therapy with ICB in melanoma and renal cell carcinoma (Cabrita et al., 2020; Helmink et al., 2020).”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Cabrita et al., 2020
Cites
In silico prediction of protein-protein interactions in human macrophages
Souiai, O., Guerfali, F. Z., Miled, S. B., Brun, C., & Benkahla, A. (2014) · BMC Research Notes · doi:10.1186/1756-0500-7-157 · Cited by 10,785 · see citing works
Significance analysis of microarrays applied to the ionizing radiation response
Tusher, V. G., Tibshirani, R., & Chu, G. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.091062498 · Cited by 10,568 · see citing works
Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown
Pertea, M., Kim, D., Pertea, G. M., Leek, J. T., & Salzberg, S. L. (2016) · Nature Protocols · doi:10.1038/nprot.2016.095 · Cited by 6,708 · see citing works
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887 · see citing works
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944 · see citing works
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D., Hoffman, K., Wei, S. C., et al. (2018) · Science · doi:10.1126/science.aan4236 · Cited by 4,812 · see citing works
Self-citationSpatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer
Bindea, G., Mlecnik, B., Tosolini, M., Kirilovsky, A., Waldner, M. J., Obenauf, A. C., Angell, H. K., Fredriksen, T., Lafontaine, L., Berger, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.10.003 · Cited by 4,390 · see citing works
Becht, É., Giraldo, N. A., Lacroix, L., Buttard, B., Elarouci, N., Petitprez, F., Sèlves, J., Laurent‐Puig, P., Sautès‐Fridman, C., Fridman, W. H., et al. (2016) · Genome biology · doi:10.1186/s13059-016-1070-5 · Cited by 3,677 · see citing works
Genomic classification of cutaneous melanoma
Akbani, R., Akdemir, K. C., Aksoy, B. A., Albert, M., Ally, A., Amin, S. B., Arachchi, H., Arora, A., Auman, J. T., Ayala, B., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.044 · Cited by 3,151 · see citing works
Self-citationGenomic correlates of response to CTLA-4 blockade in metastatic melanoma
Van Allen, E. M., Miao, D., Schilling, B., Shukla, S. A., Blank, C., Zimmer, L., Sucker, A., Hillen, U., Geukes Foppen, M. H., Goldinger, S. M., et al. (2015) · Science · doi:10.1126/science.aad0095 · Cited by 2,839 · see citing works
Self-citationB cells and tertiary lymphoid structures promote immunotherapy response
Helmink, B. A., Reddy, S. M., Gao, J., Zhang, S., Basar, R., Thakur, R., Yizhak, K., Sade-Feldman, M., Blando, J., Han, G., et al. (2020) · Nature · doi:10.1038/s41586-019-1922-8 · Cited by 2,731 · see citing works
Self-citationTumor and Microenvironment Evolution during Immunotherapy with Nivolumab
Riaz, N., Havel, J. J., Makarov, V., Desrichard, A., Urba, W. J., Sims, J. S., Hodi, F. S., Martín-Algarra, S., Mandal, R., Sharfman, W. H., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.028 · Cited by 2,401 · see citing works
Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy
Cristescu, R., Mogg, R., Ayers, M., Albright, A., Murphy, E., Yearley, J., Sher, X., Liu, X. Q., Lu, H., Nebozhyn, M., et al. (2018) · Science · doi:10.1126/science.aar3593 · Cited by 2,301 · see citing works
Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma
Sade-Feldman, M., Yizhak, K., Bjorgaard, S. L., Ray, J. P., de Boer, C. G., Jenkins, R. W., Lieb, D. J., Chen, J. H., Frederick, D. T., Barzily-Rokni, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.038 · Cited by 2,053 · see citing works
Self-citationB cells are associated with survival and immunotherapy response in sarcoma
Petitprez, F., de Reyniès, A., Keung, E. Z., Chen, T. W.-W., Sun, C.-M., Calderaro, J., Jeng, Y.-M., Hsiao, L.-P., Lacroix, L., Bougoüin, A., et al. (2020) · Nature · doi:10.1038/s41586-019-1906-8 · Cited by 1,942 · see citing works
Self-citationTertiary lymphoid structures in the era of cancer immunotherapy
Sautès-Fridman, C., Petitprez, F., Calderaro, J., & Fridman, W. H. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0144-6 · Cited by 1,884 · see citing works
A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade
Jerby-Arnon, L., Shah, P., Cuoco, M. S., Rodman, C., Su, M.-J., Melms, J. C., Leeson, R., Kanodia, A., Mei, S., Lin, J.-R., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.006 · Cited by 1,429 · see citing works
Self-citationDynamics of B cells in germinal centres
De Silva, N. S., & Klein, U. (2015) · Nature Reviews Immunology · doi:10.1038/nri3804 · Cited by 1,084 · see citing works
Gide, T. N., Quek, C., Menzies, A. M., Tasker, A. T., Shang, P., Holst, J., Madore, J., Lim, S. Y., Velickovic, R., Wongchenko, M., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.01.003 · Cited by 1,047 · see citing works
Roh, W., Chen, P.-L., Reuben, A., Spencer, C. N., Prieto, P. A., Miller, J. P., Gopalakrishnan, V., Wang, F., Cooper, Z. A., Reddy, S. M., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah3560 · Cited by 859 · see citing works
Self-citationNeoadjuvant immune checkpoint blockade in high-risk resectable melanoma
Amaria, R. N., Reddy, S. M., Tawbi, H. A., Davies, M. A., Ross, M. I., Glitza, I. C., Cormier, J. N., Lewis, C., Hwu, W.-J., Hanna, E., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0197-1 · Cited by 835 · see citing works
Self-citationOX40 Promotes Bcl-xL and Bcl-2 Expression and Is Essential for Long-Term Survival of CD4 T Cells
Rogers, P., Song, J. J., Gramaglia, I., Killeen, N. P., & Croft, M. (2001) · Immunity · doi:10.1016/s1074-7613(01)00191-1 · Cited by 645 · see citing works
Tertiary lymphoid structures in cancer and beyond
Dieu‐Nosjean, M., Goc, J., Giraldo, N. A., Sautès‐Fridman, C., & Fridman, W. H. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.09.006 · Cited by 616 · see citing works
The Tumor Microenvironment in the Response to Immune Checkpoint Blockade Therapies
Petitprez, F., Meylan, M., de Reyniès, A., Sautès‐Fridman, C., & Fridman, W. H. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00784 · Cited by 604 · see citing works
Angelova, M., Charoentong, P., Hackl, H., Fischer, M. L., Snajder, R., Krogsdam, A., Waldner, M. J., Bindea, G., Mlecnik, B., Galon, J., et al. (2015) · Genome biology · doi:10.1186/s13059-015-0620-6 · Cited by 521 · see citing works
Analysis of array CGH data: from signal ratio to gain and loss of DNA regions
Hupé, P., Stransky, N., Thiery, J. P., Radvanyi, F., & Barillot, E. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth418 · Cited by 521 · see citing works
Lauss, M., Donia, M., Harbst, K., Andersen, R. S., Mitra, S., Rosengren, F., Salim, M., Vallon‐Christersson, J., Törngren, T., Kvist, A., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01460-0 · Cited by 481 · see citing works
Self-citationMessina, J. L., Fenstermacher, D. A., Eschrich, S., Qu, X., Berglund, A. E., Lloyd, M. C., Schell, M. J., Sondak, V. K., Weber, J. S., & Mulé, J. J. (2012) · Scientific Reports · doi:10.1038/srep00765 · Cited by 426 · see citing works
CONTRA: copy number analysis for targeted resequencing
Li, J., Lupat, R., Amarasinghe, K. C., Thompson, E. R., Doyle, M., Ryland, G. L., Tothill, R. W., Halgamuge, S. K., Campbell, I., & Gorringe, K. L. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts146 · Cited by 360 · see citing works
Relevance of immune cell and tumor microenvironment imaging in the new era of immunotherapy
Galli, F., Aguilera, J. V., Palermo, B., Markovic, S. N., Nisticò, P., & Signore, A. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01586-y · Cited by 281 · see citing works
Neogenesis of Lymphoid Structures and Antibody Responses Occur in Human Melanoma Metastases
Cipponi, A., Mercier, M., Seremet, T., Baurain, J., Théate, I., van den Oord, J., Stas, M., Boon, T., Coulie, P. G., & van Baren, N. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1377 · Cited by 259 · see citing works
APPRIS: annotation of principal and alternative splice isoforms
Rodriguez, J. M., Maietta, P., Ezkurdia, I., Pietrelli, A., Wesselink, J.-J., Lopez, G., Valencia, A., & Tress, M. L. (2013) · Nucleic Acids Research · doi:10.1093/nar/gks1058 · Cited by 232 · see citing works
Suan, D., Kräutler, N. J., Mååg, J. L. V., Butt, D., Bourne, K., Hermes, J. R., Avery, D. T., Young, C., Statham, A. L., Elliott, M., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.11.022 · Cited by 230 · see citing works
Tarte, K., Zhan, F., Vos, J. D., Klein, B., & Shaughnessy, J. D. (2003) · Blood · doi:10.1182/blood-2002-10-3161 · Cited by 215 · see citing works
Prognostic impact of B-cell density in cutaneous melanoma
Ladányi, A., Kiss, J., Mohos, A., Somlai, B., Liszkay, G., Gilde, K., Fejôs, Z., Gaudi, I., Dobos, J., & Tı́már, J. (2011) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-011-1071-x · Cited by 201 · see citing works
Tertiary Lymphoid Structure-Associated B Cells are Key Players in Anti-Tumor Immunity
Germain, C., Gnjatic, S., & Dieu‐Nosjean, M. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00067 · Cited by 158 · see citing works
NF 1‐mutated melanoma tumors harbor distinct clinical and biological characteristics
Cirenajwis, H., Lauss, M., Ekedahl, H., Törngren, T., Kvist, A., Saal, L. H., Olsson, H. L., Staaf, J., Carneiro, A., Ingvar, C., et al. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12050 · Cited by 137 · see citing works
Self-citationMolecular Profiling Reveals Low- and High-Grade Forms of Primary Melanoma
Harbst, K., Staaf, J., Lauss, M., Karlsson, A., Måsbäck, A., Johansson, I., Bendahl, P.-O., Vallon-Christersson, J., Törngren, T., Ekedahl, H., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-0343 · Cited by 105 · see citing works
Self-citationMihm, M. C., & Mulé, J. J. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0143 · Cited by 83 · see citing works
Monitoring of Technical Variation in Quantitative High-Throughput Datasets
Lauss, M., Visne, I., Kriegner, A., Ringnér, M., Jönsson, G., & Höglund, M. (2013) · Cancer Informatics · doi:10.4137/cin.s12862 · Cited by 74 · see citing works
Self-citationマウスおよびヒトはい中心におけるCCR6は記憶B細胞前駆体,光帯を明らかにする位置と主要な低抗原親和性【Powered by NICT】
Dan, S., Nike, J. K., Jesper, L. V. M., Danyal, B., Bourne, K., Jana, R., Tullman‐Ercek, D., Young, C., Aaron, S., Michael, E., et al. (2017) · Immunity · Cited by 57 · see citing works
Effects of B cell–activating factor on tumor immunity
Yarchoan, M. M., Ho, W. J., Mohan, A. A., Shah, Y., Vithayathil, T., Leatherman, J. M., Dennison, L., Zaidi, N., Ganguly, S., Woolman, S., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.136417 · Cited by 56 · see citing works
Ryan, S. T., Zhang, J., Burner, D. N., Liss, M. A., Pittman, E. I., Muldong, M. T., Shabaik, A. S., Woo, J. R., Bassler, N., Cunha, J., et al. (2020) · Journal of Translational Medicine · doi:10.1186/s12967-020-02370-4 · Cited by 37 · see citing works
Circular RNA and tumor microenvironment
Song, H., Liu, Q., & Liao, Q. (2020) · Cancer Cell International · doi:10.1186/s12935-020-01301-z · Cited by 36 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
B cells and tertiary lymphoid structures promote immunotherapy response
Helmink, B. A., Reddy, S. M., Gao, J., Zhang, S., Basar, R., Thakur, R., Yizhak, K., Sade-Feldman, M., Blando, J., Han, G., et al. (2020) · Nature · doi:10.1038/s41586-019-1922-8 · Cited by 2,731 · see citing works
Self-citationHallmarks of response, resistance, and toxicity to immune checkpoint blockade
Morad, G., Helmink, B. A., Sharma, P., & Wargo, J. A. (2021) · Cell · doi:10.1016/j.cell.2021.09.020 · Cited by 1,648 · see citing works
Self-citationThe immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy
Bruni, D., Angell, H. K., & Galon, J. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0285-7 · Cited by 1,586 · see citing works
Meylan, M., Petitprez, F., Becht, E., Bougoüin, A., Pupier, G., Calvez, A., Giglioli, I., Verkarre, V., Lacroix, G., Verneau, J., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.02.001 · Cited by 831 · see citing works
Zhang, Y., Chen, H., Mo, H., Hu, X., Gao, R., Zhao, Y., Liu, B., Niu, L., Sun, X., Yu, X., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.09.010 · Cited by 783 · see citing works
Turning cold tumors hot: from molecular mechanisms to clinical applications
Zhang, J., Huang, D., Saw, P. E., & Song, E. (2022) · Trends in Immunology · doi:10.1016/j.it.2022.04.010 · Cited by 534 · see citing works
Fu, T., Dai, L.-J., Wu, S.-Y., Xiao, Y., Ma, D., Jiang, Y.-Z., & Shao, Z.-M. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01103-4 · Cited by 480 · see citing works
Andersson, A., Larsson, L., Stenbeck, L., Salmén, F., Ehinger, A., Wu, S. Z., Al-Eryani, G., Roden, D., Swarbrick, A., Borg, Å., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26271-2 · Cited by 404 · see citing works
Magen, A., Hamon, P., Fiaschi, N., Soong, B. Y., Park, M. D., Mattiuz, R., Humblin, E., Troncoso, L., D’souza, D., Dawson, T., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02345-0 · Cited by 429 · see citing works
Grasso, C. S., Tsoi, J., Onyshchenko, M., Abril-Rodriguez, G., Ross-Macdonald, P., Wind-Rotolo, M., Champhekar, A., Medina, E., Torrejon, D. Y., Shin, D. S., et al. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.08.005 · Cited by 390 · see citing works
An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer
Voabil, P., de Bruijn, M., Roelofsen, L. M., Hendriks, S. H., Brokamp, S., van den Braber, M., Broeks, A., Sanders, J., Herzig, P., Zippelius, A., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01398-3 · Cited by 380 · see citing works
Ho, W. J., Zhu, Q., Durham, J., Popovic, A., Xavier, S., Leatherman, J., Mohan, A., Mo, G., Zhang, S., Gross, N., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00234-4 · Cited by 360 · see citing works
Role of B cells as antigen presenting cells
Rastogi, I., Jeon, D., Moseman, J. E., Muralidhar, A., Potluri, H. K., & McNeel, D. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.954936 · Cited by 352 · see citing works
Moving towards personalized treatments of immune-related adverse events
Esfahani, K., Elkrief, A., Calabrese, C., Lapointe, R., Hudson, M., Routy, B., Miller, W. H., & Calabrese, L. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0352-8 · Cited by 351 · see citing works
Gao, J., Navai, N., Alhalabi, O., Siefker-Radtke, A., Campbell, M. T., Tidwell, R. S., Guo, C. C., Kamat, A. M., Matin, S. F., Araujo, J. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1086-y · Cited by 318 · see citing works
Overacre-Delgoffe, A. E., Bumgarner, H. J., Cillo, A. R., Burr, A. H. P., Tometich, J. T., Bhattacharjee, A., Bruno, T. C., Vignali, D. A. A., & Hand, T. W. (2021) · Immunity · doi:10.1016/j.immuni.2021.11.003 · Cited by 318 · see citing works
Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy
Gohil, S. H., Iorgulescu, J. B., Braun, D. A., Keskin, D. B., & Livak, K. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00449-x · Cited by 282 · see citing works
Hammerl, D., Martens, J. W. M., Timmermans, M., Smid, M., Trapman-Jansen, A. M., Foekens, R., Isaeva, O. I., Voorwerk, L., Balcioglu, H. E., Wijers, R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25962-0 · Cited by 262 · see citing works
Wang, Y., Tong, Z., Zhang, W., Zhang, W., Buzdin, A., Mu, X., Yan, Q., Zhao, X., Chang, H.-H., Duhon, M., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.683419 · Cited by 224 · see citing works
MIF-Dependent Control of Tumor Immunity
Noe, J. T., & Mitchell, R. A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.609948 · Cited by 198 · see citing works
T cell factor 1: A master regulator of the T cell response in disease
Escobar, G., Mangani, D., & Anderson, A. C. (2020) · Science Immunology · doi:10.1126/sciimmunol.abb9726 · Cited by 211 · see citing works
Hu, Q., Hong, Y., Qi, P., Lu, G., Mai, X., Xu, S., He, X., Guo, Y., Gao, L., Jing, Z., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22300-2 · Cited by 201 · see citing works
Liudahl, S. M., Betts, C. B., Sivagnanam, S., Morales-Oyarvide, V., da Silva, A., Yuan, C., Hwang, S., Grossblatt-Wait, A., Leis, K. R., Larson, W., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0841 · Cited by 164 · see citing works
Goswami, S., Chen, Y., Anandhan, S., Szabo, P. M., Basu, S., Blando, J. M., Liu, W., Zhang, J., Natarajan, S. M., Xiong, L., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abc4220 · Cited by 133 · see citing works
Combined Inhibition of SHP2 and CXCR1/2 Promotes Antitumor T-cell Response in NSCLC
Tang, K. H., Li, S., Khodadadi-Jamayran, A., Jen, J., Han, H., Guidry, K., Chen, T., Hao, Y., Fedele, C., Zebala, J. A., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0369 · Cited by 105 · see citing works
Wang, L., Sfakianos, J. P., Beaumont, K. G., Akturk, G., Horowitz, A., Sebra, R. P., Farkas, A. M., Gnjatic, S., Hake, A., Izadmehr, S., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4574 · Cited by 97 · see citing works
Epigenetic state determines the in vivo efficacy of STING agonist therapy
Falahat, R., Berglund, A., Perez-Villarroel, P., Putney, R. M., Hamaidi, I., Kim, S., Pilon-Thomas, S., Barber, G. N., & Mulé, J. J. (2023) · Nature Communications · doi:10.1038/s41467-023-37217-1 · Cited by 94 · see citing works
Goubet, A.-G., Lordello, L., Alves Costa Silva, C., Peguillet, I., Gazzano, M., Mbogning-Fonkou, M. D., Thelemaque, C., Lebacle, C., Thibault, C., Audenet, F., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0201 · Cited by 86 · see citing works
Hosein, A. N., Dangol, G., Okumura, T., Roszik, J., Rajapakshe, K., Siemann, M., Zaid, M., Ghosh, B., Monberg, M., Guerrero, P. A., et al. (2022) · Gastroenterology · doi:10.1053/j.gastro.2021.12.273 · Cited by 61 · see citing works
The 12-CK Score: Global Measurement of Tertiary Lymphoid Structures
Li, R., Berglund, A., Zemp, L., Dhillon, J., Putney, R., Kim, Y., Jain, R. K., Grass, G. D., Conejo-Garcia, J., & Mulé, J. J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.694079 · Cited by 39 · see citing works
Refining patient selection for breast cancer immunotherapy: beyond PD-L1
Kossai, M., Radosevic-Robin, N., & Penault-Llorca, F. (2021) · ESMO Open · doi:10.1016/j.esmoop.2021.100257 · Cited by 36 · see citing works
Jammihal, T., Saliby, R. M., Labaki, C., Soulati, H., Gallegos, J., Peris, A., McCurry, D., Yu, C., Shah, V., Poduval, D., et al. (2025) · Nature Cancer · doi:10.1038/s43018-024-00896-w · Cited by 38 · see citing works
Li, G.-Q., Wang, Y.-K., Zhou, H., Jin, L.-G., Wang, C.-Y., Albahde, M., Wu, Y., Li, H.-Y., Zhang, W.-K., Li, B.-H., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.630355 · Cited by 24 · see citing works
Wang, Y., Ju, X., Hua, R., Chen, J., Dai, X., Liu, L., Wang, G., Bai, Y., Hu, H., & Li, X. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02856-8 · Cited by 18 · see citing works
Seethapathy, H., Mistry, K., & Sise, M. E. (2023) · Immunological Reviews · doi:10.1111/imr.13243 · Cited by 15 · see citing works
- Authors
- Cabrita, R., Lauss, M., Sanna, A., Donia, M., Skaarup Larsen, M., Mitra, S., Johansson, I., Phung, B., Harbst, K., Vallon-Christersson, J., van Schoiack, A., Lövgren, K., Warren, S., Jirström, K., Olsson, H., Pietras, K., Ingvar, C., Isaksson, K., Schadendorf, D., Schmidt, H., Bastholt, L., Carneiro, A., Wargo, J. A., Svane, I. M., & Jönsson, G.
- Affiliations
- Lund University (SE)
- Herlev Hospital (DK)
- Nanostring Technologies (United States) (US)
- Skåne University Hospital (SE)
- Essen University Hospital (DE)
- Aarhus University Hospital (DK)
- Odense University Hospital (DK)
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Venue
- Nature
- Published
- 2020-01-15
- Volume
- 577
- Issue
- 7791
- Pages
- 561-565
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3000311037
- Cited by
- 2,374
- References
- 44
- Citations by year
- 2026: 330 · 2025: 382 · 2024: 445 · 2023: 344 · 2022: 352 · 2021: 352 · 2020: 167 · 2019: 1
- FWCI
- 110.35
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-03-20)
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Funders
- European Commission (641458, H2020-MSCA-ITN, H2020-MSCA-ITN-2014, HORIZON2020, H2020, H2020-MSCA, 247634)
- Horizon 2020 Framework Programme (H2020MSCA‐ITN‐2014, H2020-MSCA, 247634, 641458, H2020-MSCA-ITN)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- tertiary lymphoid structures, metastatic melanoma, immune checkpoint blockade, B cells, CD8+ T cells, CD20, CXCR5, CXCL13, tumor immune microenvironment, T cell phenotype, TCF1, gene expression signatures, survival prediction, cancer immunotherapy response
- MeSH terms
- Tertiary Lymphoid Structures, RNA-Seq, B-Lymphocytes, Humans, Immunologic Memory, Melanoma, Neoplasm Metastasis, Phenotype, Prognosis, T-Lymphocytes, Survival Rate, Treatment Outcome, CD8-Positive T-Lymphocytes, Antigens, CD20, Proteomics, T Cell Transcription Factor 1, Receptors, CXCR5, Chemokine CXCL13, Single-Cell Analysis, Tumor Microenvironment, B7-H1 Antigen, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
