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9. LGR5 in breast cancer and ductal carcinoma in situ: a diagnostic and prognostic biomarker and a therapeutic target

Author

Hagerling, Catharina, Owyong, Mark, Sitarama, Vaishnavi, Wang, Chih-Yang, Lin, Charlene, van den Bijgaart, Renske JE, Koopman, Charlotte D, Brenot, Audrey, Nanjaraj, Ankitha, Wärnberg, Fredrik, Jirström, Karin, Klein, Ophir D, Werb, Zena, and Plaks, Vicki

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Breast Cancer, Biotechnology, Prevention, Cancer, Adult, Aged, Aged, 80 and over, Animals, Biomarkers, Tumor, Breast Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Cell Line, Tumor, Female, Heterografts, Humans, Mice, Middle Aged, Prognosis, RNA, Neoplasm, Real-Time Polymerase Chain Reaction, Receptor, ErbB-2, Receptors, G-Protein-Coupled, Tissue Array Analysis, LGR5, Breast cancer, DCIS, Estrogen receptor, Targeted therapy, Receptor, erbB-2, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis, Epidemiology
Abstract

BackgroundNovel biomarkers are required to discern between breast tumors that should be targeted for treatment from those that would never become clinically apparent and/or life threatening for patients. Moreover, therapeutics that specifically target breast cancer (BC) cells with tumor-initiating capacity to prevent recurrence are an unmet need. We investigated the clinical importance of LGR5 in BC and ductal carcinoma in situ (DCIS) to explore LGR5 as a biomarker and a therapeutic target.MethodsWe stained BC (n = 401) and DCIS (n = 119) tissue microarrays with an antibody against LGR5. We examined an LGR5 knockdown ER- cell line that was orthotopically transplanted and used for in vitro colony assays. We also determined the tumor-initiating role of Lgr5 in lineage-tracing experiments. Lastly, we transplanted ER- patient-derived xenografts into mice that were subsequently treated with a LGR5 antibody drug conjugate (anti-LGR5-ADC).ResultsLGR5 expression correlated with small tumor size, lower grade, lymph node negativity, and ER-positivity. ER+ patients with LGR5high tumors rarely had recurrence, while high-grade ER- patients with LGR5high expression recurred and died due to BC more often. Intriguingly, all the DCIS patients who later died of BC had LGR5-positive tumors. Colony assays and xenograft experiments substantiated a role for LGR5 in ER- tumor initiation and subsequent growth, which was further validated by lineage-tracing experiments in ER- /triple-negative BC mouse models. Importantly, by utilizing LGR5high patient-derived xenografts, we showed that anti-LGR5-ADC should be considered as a therapeutic for high-grade ER- BC.ConclusionLGR5 has distinct roles in ER- vs. ER+ BC with potential clinical applicability as a biomarker to identify patients in need of therapy and could serve as a therapeutic target for high-grade ER- BC.

Published
2020

13. High Caveolin-1 mRNA expression in triple-negative breast cancer is associated with an aggressive tumor microenvironment, chemoresistance, and poor clinical outcome.

Author

Godina, Christopher, Khazaei, Somayeh, Belting, Mattias, Vallon-Christersson, Johan, Nodin, Björn, Jirström, Karin, Isaksson, Karolin, Bosch, Ana, and Jernström, Helena

Subjects
TRIPLE-negative breast cancer, TREATMENT effectiveness, TUMOR microenvironment, GENE expression, CAVEOLINS
Abstract

Background: Currently, there are few treatment-predictive and prognostic biomarkers in triple-negative breast cancer (TNBC). Caveolin-1 (CAV1) is linked to chemoresistance and several important processes involved in tumor progression and metastasis, such as epithelial-mesenchymal transition (EMT). Herein, we report that high CAV1 gene expression is an independent factor of poor prognosis in TNBC. Methods: CAV1 gene expression was compared across different molecular features (e.g., PAM50 subtypes). CAV1 expression was assessed in relation to clinical outcomes using Cox regression adjusted for clinicopathological predictors. Differential gene expression and gene set enrichment analyses were applied to compare high- and low-expressing CAV1 tumors. Tumor microenvironment composition of high- and low-expressing CAV1 tumors was estimated using ECOTYPER. Tumor tissue microarrays were used to evaluate CAV1 protein levels in stromal and malignant cells. Results: In the SCAN-B (n = 525) and GSE31519 (n = 327) cohorts, patients with CAV1-high tumors had an increased incidence of early recurrence adjusted HR 1.78 (95% CI 1.12–2.81) and 2.20 (95% CI 1.39–3.47), respectively. In further analysis, high CAV1 gene expression was associated with a molecular profile indicating altered metabolism, neovascularization, chemoresistance, EMT, suppressed immune response, and active tumor microenvironment. Protein levels of CAV1 in malignant and stromal cells were not correlated with CAV1 gene expression. Conclusion: CAV1 gene expression in TNBC is a biomarker that merits further investigation in clinical trials and as a therapeutic target. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers.

Author

Allaoui, Roni, Bergenfelz, Caroline, Mohlin, Sofie, Hagerling, Catharina, Salari, Kiarash, Werb, Zena, Anderson, Robin L, Ethier, Stephen P, Jirström, Karin, Påhlman, Sven, Bexell, Daniel, Tahin, Balázs, Johansson, Martin E, Larsson, Christer, and Leandersson, Karin

Subjects
Monocytes, Cell Line, Tumor, Stromal Cells, Myeloid Cells, Animals, Humans, Mice, Nude, Collagen, Chemotactic Factors, Immunosuppression, Coculture Techniques, Xenograft Model Antitumor Assays, Gene Expression Profiling, Cell Proliferation, Cell Survival, Gene Expression Regulation, Neoplastic, Solubility, Female, Tumor Microenvironment, Triple Negative Breast Neoplasms, Cancer-Associated Fibroblasts, Chemokine CXCL16, Cell Line, Tumor, Mice, Nude, Gene Expression Regulation, Neoplastic, Cancer, Breast Cancer, 2.1 Biological and endogenous factors
Abstract

Triple-negative (TN) breast cancers (ER-PR-HER2-) are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance.

Published
2016

19. Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Author

Cabrita, Rita, Lauss, Martin, Sanna, Adriana, Donia, Marco, Skaarup Larsen, Mathilde, Mitra, Shamik, Johansson, Iva, Phung, Bengt, Harbst, Katja, Vallon-Christersson, Johan, van Schoiack, Alison, Lövgren, Kristina, Warren, Sarah, Jirström, Karin, Olsson, Håkan, Pietras, Kristian, Ingvar, Christian, Isaksson, Karolin, Schadendorf, Dirk, Schmidt, Henrik, Bastholt, Lars, Carneiro, Ana, Wargo, Jennifer A., Svane, Inge Marie, and Jönsson, Göran

Published
2020
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21. AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation.

Author

Källberg, Eva, Mehmeti-Ajradini, Meliha, Björk Gunnarsdottir, Frida, Göransson, Marcus, Bergenfelz, Caroline, Allaoui Fredriksson, Roni, Hagerling, Catharina, Johansson, Martin E, Welinder, Charlotte, Jirström, Karin, and Leandersson, Karin

Subjects
BREAST cancer, CELL death, DEATH receptors, CANCER cells, INFLAMMATION
Abstract

The autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymus and is necessary for maintaining immunological self-tolerance. Extrathymic AIRE expression is rare, and a role for AIRE in tumor-associated innate immune cells has not yet been established. In this study, we show that AIRE is expressed in human pro-tumor neutrophils. In breast cancer, AIRE was primarily located to tumor-associated neutrophils (TANs), and to a lesser extent to tumor-associated macrophages (TAMs) and tumor cells. Expression of AIRE in TAN/TAMs, but not in cancer cells, was associated with an adverse prognosis. We show that the functional role for AIRE in neutrophils and macrophages is to regulate expression of immune mediators and the extrinsic apoptotic pathway involving the Fas/TNFR death receptors and cathepsin G. Here, we propose that the role for AIRE in TAN/TAMs in breast tumors is to regulate cell death and inflammation, thus promoting tumor progression. The immune tolerance protein autoimmune regulator (AIRE) is here shown to be expressed in breast tumor infiltrating neutrophils and macrophages to regulate extrinsic apoptotic pathways. [ABSTRACT FROM AUTHOR]

Published
2024
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22. AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation

Author

Källberg, Eva, primary, Mehmeti-Ajradini, Meliha, additional, Gunnarsdottir, Frida Björk, additional, Göransson, Marcus, additional, Bergenfelz, Caroline, additional, Fredriksson, Roni Allaoui, additional, Hagerling, Catharina, additional, Johansson, Martin E, additional, Welinder, Charlotte, additional, Jirström, Karin, additional, and Leandersson, Karin, additional

Published
2023
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23. Table S3 from Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution

Author

Rastegar, Bahar, primary, Andersson, Natalie, primary, Petersson, Alexandra, primary, Karlsson, Jenny, primary, Chattopadhyay, Subhayan, primary, Valind, Anders, primary, Jansson, Caroline, primary, Durand, Geoffroy, primary, Romerius, Patrik, primary, Jirström, Karin, primary, Holmquist Mengelbier, Linda, primary, and Gisselsson, David, primary

Published
2023
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24. Figure S1 from Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution

Author

Rastegar, Bahar, primary, Andersson, Natalie, primary, Petersson, Alexandra, primary, Karlsson, Jenny, primary, Chattopadhyay, Subhayan, primary, Valind, Anders, primary, Jansson, Caroline, primary, Durand, Geoffroy, primary, Romerius, Patrik, primary, Jirström, Karin, primary, Holmquist Mengelbier, Linda, primary, and Gisselsson, David, primary

Published
2023
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25. Data from Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution

Author

Rastegar, Bahar, primary, Andersson, Natalie, primary, Petersson, Alexandra, primary, Karlsson, Jenny, primary, Chattopadhyay, Subhayan, primary, Valind, Anders, primary, Jansson, Caroline, primary, Durand, Geoffroy, primary, Romerius, Patrik, primary, Jirström, Karin, primary, Holmquist Mengelbier, Linda, primary, and Gisselsson, David, primary

Published
2023
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31. Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution

Author

Rastegar, Bahar, primary, Andersson, Natalie, additional, Petersson, Alexandra, additional, Karlsson, Jenny, additional, Chattopadhyay, Subhayan, additional, Valind, Anders, additional, Jansson, Caroline, additional, Durand, Geoffroy, additional, Romerius, Patrik, additional, Jirström, Karin, additional, Holmquist Mengelbier, Linda, additional, and Gisselsson, David, additional

Published
2023
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33. Spatial immunophenotyping of the tumour microenvironment in non–small cell lung cancer

Author

Backman, Max, primary, Strell, Carina, additional, Lindberg, Amanda, additional, Mattsson, Johanna S.M., additional, Elfving, Hedvig, additional, Brunnström, Hans, additional, O'Reilly, Aine, additional, Bosic, Martina, additional, Gulyas, Miklos, additional, Isaksson, Johan, additional, Botling, Johan, additional, Kärre, Klas, additional, Jirström, Karin, additional, Lamberg, Kristina, additional, Pontén, Fredrik, additional, Leandersson, Karin, additional, Mezheyeuski, Artur, additional, and Micke, Patrick, additional

Published
2023
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34. Data from Branching Copy-Number Evolution and Parallel Immune Profiles across the Regional Tumor Space of Resected Pancreatic Cancer

Author

Petersson, Alexandra, primary, Andersson, Natalie, primary, Hau, Sofie Olsson, primary, Eberhard, Jakob, primary, Karlsson, Jenny, primary, Chattopadhyay, Subhayan, primary, Valind, Anders, primary, Elebro, Jacob, primary, Nodin, Björn, primary, Leandersson, Karin, primary, Gisselsson, David, primary, and Jirström, Karin, primary

Published
2023
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35. Supplementary Data from Branching Copy-Number Evolution and Parallel Immune Profiles across the Regional Tumor Space of Resected Pancreatic Cancer

Author

Petersson, Alexandra, primary, Andersson, Natalie, primary, Hau, Sofie Olsson, primary, Eberhard, Jakob, primary, Karlsson, Jenny, primary, Chattopadhyay, Subhayan, primary, Valind, Anders, primary, Elebro, Jacob, primary, Nodin, Björn, primary, Leandersson, Karin, primary, Gisselsson, David, primary, and Jirström, Karin, primary

Published
2023
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36. Supplementary Fig. 6 from Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1

Author

Indira Chandran, Vineesh, primary, Månsson, Ann-Sofie, primary, Barbachowska, Magdalena, primary, Cerezo-Magaña, Myriam, primary, Nodin, Björn, primary, Joshi, Bharat, primary, Koppada, Neelima, primary, Saad, Ola M., primary, Gluz, Oleg, primary, Isaksson, Karolin, primary, Borgquist, Signe, primary, Jirström, Karin, primary, Nabi, Ivan Robert, primary, Jernström, Helena, primary, and Belting, Mattias, primary

Published
2023
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37. Supplementary Table 1 from Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1

Author

Indira Chandran, Vineesh, primary, Månsson, Ann-Sofie, primary, Barbachowska, Magdalena, primary, Cerezo-Magaña, Myriam, primary, Nodin, Björn, primary, Joshi, Bharat, primary, Koppada, Neelima, primary, Saad, Ola M., primary, Gluz, Oleg, primary, Isaksson, Karolin, primary, Borgquist, Signe, primary, Jirström, Karin, primary, Nabi, Ivan Robert, primary, Jernström, Helena, primary, and Belting, Mattias, primary

Published
2023
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38. Supplementary Fig. 1 from Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1

Author

Indira Chandran, Vineesh, primary, Månsson, Ann-Sofie, primary, Barbachowska, Magdalena, primary, Cerezo-Magaña, Myriam, primary, Nodin, Björn, primary, Joshi, Bharat, primary, Koppada, Neelima, primary, Saad, Ola M., primary, Gluz, Oleg, primary, Isaksson, Karolin, primary, Borgquist, Signe, primary, Jirström, Karin, primary, Nabi, Ivan Robert, primary, Jernström, Helena, primary, and Belting, Mattias, primary

Published
2023
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39. Data from Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1

Author

Indira Chandran, Vineesh, primary, Månsson, Ann-Sofie, primary, Barbachowska, Magdalena, primary, Cerezo-Magaña, Myriam, primary, Nodin, Björn, primary, Joshi, Bharat, primary, Koppada, Neelima, primary, Saad, Ola M., primary, Gluz, Oleg, primary, Isaksson, Karolin, primary, Borgquist, Signe, primary, Jirström, Karin, primary, Nabi, Ivan Robert, primary, Jernström, Helena, primary, and Belting, Mattias, primary

Published
2023
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40. Data from Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy

Author

DeNardo, David G., primary, Brennan, Donal J., primary, Rexhepaj, Elton, primary, Ruffell, Brian, primary, Shiao, Stephen L., primary, Madden, Stephen F., primary, Gallagher, William M., primary, Wadhwani, Nikhil, primary, Keil, Scott D., primary, Junaid, Sharfaa A., primary, Rugo, Hope S., primary, Hwang, E. Shelley, primary, Jirström, Karin, primary, West, Brian L., primary, and Coussens, Lisa M., primary

Published
2023
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41. Supplementary Fig. 5 from Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1

Author

Indira Chandran, Vineesh, primary, Månsson, Ann-Sofie, primary, Barbachowska, Magdalena, primary, Cerezo-Magaña, Myriam, primary, Nodin, Björn, primary, Joshi, Bharat, primary, Koppada, Neelima, primary, Saad, Ola M., primary, Gluz, Oleg, primary, Isaksson, Karolin, primary, Borgquist, Signe, primary, Jirström, Karin, primary, Nabi, Ivan Robert, primary, Jernström, Helena, primary, and Belting, Mattias, primary

Published
2023
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42. Supplementary Methods, Figures 1-10, Tables 1-8 from Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy

Author

DeNardo, David G., primary, Brennan, Donal J., primary, Rexhepaj, Elton, primary, Ruffell, Brian, primary, Shiao, Stephen L., primary, Madden, Stephen F., primary, Gallagher, William M., primary, Wadhwani, Nikhil, primary, Keil, Scott D., primary, Junaid, Sharfaa A., primary, Rugo, Hope S., primary, Hwang, E. Shelley, primary, Jirström, Karin, primary, West, Brian L., primary, and Coussens, Lisa M., primary

Published
2023
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43. Supplementary Fig. 7 from Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1

Author

Indira Chandran, Vineesh, primary, Månsson, Ann-Sofie, primary, Barbachowska, Magdalena, primary, Cerezo-Magaña, Myriam, primary, Nodin, Björn, primary, Joshi, Bharat, primary, Koppada, Neelima, primary, Saad, Ola M., primary, Gluz, Oleg, primary, Isaksson, Karolin, primary, Borgquist, Signe, primary, Jirström, Karin, primary, Nabi, Ivan Robert, primary, Jernström, Helena, primary, and Belting, Mattias, primary

Published
2023
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44. Supplementary Fig. 2 from Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1

Author

Indira Chandran, Vineesh, primary, Månsson, Ann-Sofie, primary, Barbachowska, Magdalena, primary, Cerezo-Magaña, Myriam, primary, Nodin, Björn, primary, Joshi, Bharat, primary, Koppada, Neelima, primary, Saad, Ola M., primary, Gluz, Oleg, primary, Isaksson, Karolin, primary, Borgquist, Signe, primary, Jirström, Karin, primary, Nabi, Ivan Robert, primary, Jernström, Helena, primary, and Belting, Mattias, primary

Published
2023
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45. Supplementary Fig. 3 from Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1

Author

Indira Chandran, Vineesh, primary, Månsson, Ann-Sofie, primary, Barbachowska, Magdalena, primary, Cerezo-Magaña, Myriam, primary, Nodin, Björn, primary, Joshi, Bharat, primary, Koppada, Neelima, primary, Saad, Ola M., primary, Gluz, Oleg, primary, Isaksson, Karolin, primary, Borgquist, Signe, primary, Jirström, Karin, primary, Nabi, Ivan Robert, primary, Jernström, Helena, primary, and Belting, Mattias, primary

Published
2023
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46. Supplementary Fig. 4 from Hypoxia Attenuates Trastuzumab Uptake and Trastuzumab-Emtansine (T-DM1) Cytotoxicity through Redistribution of Phosphorylated Caveolin-1

Author

Indira Chandran, Vineesh, primary, Månsson, Ann-Sofie, primary, Barbachowska, Magdalena, primary, Cerezo-Magaña, Myriam, primary, Nodin, Björn, primary, Joshi, Bharat, primary, Koppada, Neelima, primary, Saad, Ola M., primary, Gluz, Oleg, primary, Isaksson, Karolin, primary, Borgquist, Signe, primary, Jirström, Karin, primary, Nabi, Ivan Robert, primary, Jernström, Helena, primary, and Belting, Mattias, primary

Published
2023
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47. Spatial immunophenotyping of the tumour microenvironment in non-small cell lung cancer

Author

Backman, Max, Strell, Carina, Lindberg, Amanda, Mattsson, Johanna S. M., Elfving, Hedvig, Brunnström, Hans, O'Reilly, Aine, Bosic, Martina, Gulyas, Miklos, Isaksson, Johan, Botling, Johan, Kärre, Klas, Jirström, Karin, Lamberg, Kristina, Pontén, Fredrik, Leandersson, Karin, Mezheyeuski, Artur, Micke, Patrick, Backman, Max, Strell, Carina, Lindberg, Amanda, Mattsson, Johanna S. M., Elfving, Hedvig, Brunnström, Hans, O'Reilly, Aine, Bosic, Martina, Gulyas, Miklos, Isaksson, Johan, Botling, Johan, Kärre, Klas, Jirström, Karin, Lamberg, Kristina, Pontén, Fredrik, Leandersson, Karin, Mezheyeuski, Artur, and Micke, Patrick

Abstract

Introduction: Immune cells in the tumour microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterise the spatial im-mune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC). Methods: We established a multiplexed fluorescence imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4-Eff), CD4 regulatory cells (CD4-Treg), CD8 effector cells (CD8-Eff), CD8 regulatory cells (CD8-Treg), B-cells, natural killer cells, natural killer T-cells, M1 macrophages (M1), CD163 thorn myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). Results: CD4-Eff cells, CD8-Eff cells and M1 macrophages were the most abundant immune cells invading the tumour cell compartment and indicated a patient group with a favourable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4-Eff, CD4-Treg, CD8-Treg, B-cells and pDCs) were independently associated with longer survival. However, when these immune cells were located close to CD8-Treg cells, the favourable impact was attenuated. In the multivariable Cox regression model, including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8-Treg-B-cells, CD8-Eff-cancer cells and B-cells-CD4-Treg) demonstrated positive prognostic impact, whereas short M2-M1 distances were prognostically unfavourable. Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is crucial for diagnostic use., De två sista författarna delar sistaförfattarskapet

Published
2023
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