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Mattsson, Johanna Sofia MargaretaORCID iD iconorcid.org/0000-0002-5294-7808
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Publications (10 of 36) Show all publications
Tsakonas, G., Botling, J., Micke, P., Rivard, C., La Fleur, L., Mattsson, J. S., . . . Ekman, S. (2019). c-MET as a biomarker in patients with surgically resected non-small cell lung cancer. Lung Cancer, 133, 69-74
Open this publication in new window or tab >>c-MET as a biomarker in patients with surgically resected non-small cell lung cancer
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2019 (English)In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 133, p. 69-74Article in journal (Refereed) Published
Abstract [en]

Background: c-MET protein overexpression has been proposed as a biomarker in non-small cell lung cancer (NSCLC), albeit its role in the clinical setting has not been firmly established yet. Patients and methods: We designed a retrospective cohort study, consisting of 725 patients with surgically removed NSCLC. Immunohistochemistry (IHC) was conducted in tissue microarrays (TMA) from lung tumors and healthy tissue. IHC staining was quantified using H-scores (range 0-300). Association between c-MET H-score and overall survival (OS) as well as progression-free survival (PFS) was explored. Results: c-MET H-score >= 20 had a significant positive impact on OS in the multivariate analysis in the whole study population, HR = 0.79 (95%CI: 0.64 - 0.97). The prognostic effect of c-MET H-score >= 20 was even stronger in patients who received adjuvant treatment with a HR = 0.61 (95% CI: 0.40 - 0.93). In the subgroup of adenocarcinoma and squamous cell carcinoma patients with stage IIA-IIIB disease, the prognostic impact of c-MET was significant in the univariate analysis (HR = 0.60, 95% CI: 0.43 - 0.83). Conclusion: c-MET H-score >= 20 is a positive prognostic biomarker for OS in early stage NSCLC. This benefit seems to be strongly correlated to adjuvant chemotherapy, therefore rendering c-MET H-score >= 20 a possible predictive biomarker for platinum-based adjuvant chemotherapy in early stage NSCLC.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
c-MET, Lung cancer, Biomarker, OS, PFS, H-score
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-390909 (URN)10.1016/j.lungcan.2019.04.028 (DOI)000474326700012 ()31200831 (PubMedID)
Funder
Stockholm County Council
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2020-01-08Bibliographically approved
Vidarsdottir, H., Tran, L., Nodin, B., Jirström, K., Planck, M., Jönsson, P., . . . Brunnström, H. (2019). Immunohistochemical profiles in primary lung cancers and epithelial pulmonary metastases. Human Pathology, 84, 221-230
Open this publication in new window or tab >>Immunohistochemical profiles in primary lung cancers and epithelial pulmonary metastases
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2019 (English)In: Human Pathology, ISSN 0046-8177, E-ISSN 1532-8392, Vol. 84, p. 221-230Article in journal (Refereed) Published
Abstract [en]

Correct diagnosis of pulmonary tumors is essential for treatment decision and often rely on immunohistochemical markers. We stained tissue microarrays from resected primary lung cancer (n=665) and pulmonary metastases (n=425) for CK7, CK20, CDX2, CK5, p40, p63, TTF-1, napsin A, GATA3 and PAX8 to systematically assess the diagnostic value of these markers. Primary lung adenocarcinomas expressed TTF-1 in 90% and napsin A in 84% of the cases, while 10% were positive for p63, 7% for CDX2, 2% for CK20 and 2% for GATA3. Only 68% of the lung adenocarcinomas were positive for CK7, TTF-1 and napsin A and negative for all other markers. Primary lung squamous cell carcinomas expressed CK5, p40 and p63 in 94-97% of cases, while 44% were positive for CK7, 20% for GATA3, 7% for CDX2 and 3% for TTF-1. Rare cases expressed PAX8, CK20 or napsin A. Pulmonary metastases of colorectal cancer were positive for CK20 in 83% and CDX2 in 99% of the cases. Rare cases expressed CK7, p63 or PAX8, while 4% expressed TTF-1. Pulmonary metastases of renal cell carcinomas were positive for PAX8 in 74%, napsin A in 7% and CK7 in 7% of the cases. Pulmonary metastases of breast cancer were positive for GATA3 in 93% and CK7 in 78% of the cases, while 15% expressed CK5. Information on expression and patterns of immunohistochemical markers facilitates histopathological diagnostics. Evidently, unusual immune profiles occur and may lead to incorrect diagnosis.

Keywords
CDX2, Cytokeratin, GATA3, Napsin a, TTF-1, Tissue Microarray
National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372013 (URN)10.1016/j.humpath.2018.10.009 (DOI)000461725100025 ()30389437 (PubMedID)
Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2020-01-03Bibliographically approved
Micke, P., Botling, J., Mattsson, J. S., Planck, M., Tran, L., Vidarsdottir, H., . . . Brunnstrom, H. (2019). Mucin staining is of limited value in addition to basic immunohistochemical analyses in the diagnostics of non-small cell lung cancer. Scientific Reports, 9, Article ID 1319.
Open this publication in new window or tab >>Mucin staining is of limited value in addition to basic immunohistochemical analyses in the diagnostics of non-small cell lung cancer
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1319Article in journal (Refereed) Published
Abstract [en]

Accurate diagnosis of histological type is important for therapy selection in lung cancer. Immunohistochemical (IHC) and histochemical stains are often used to complement morphology for definite diagnosis and are incorporated in the WHO classification. Our main aim was to compare different mucin stains and assess their value in relation to common IHC analyses in lung cancer diagnostics. Using tissue microarrays from 657 surgically treated primary lung cancers, we evaluated the mucin stains periodic acid-Schiff with diastase (PASD), alcian blue-periodic acid-Schiff (ABPAS) and mucicarmine, and compared with the IHC markers p40, p63, cytokeratin 5, thyroid transcription factor 1 (TTF-1), napsin A and cytokeratin 7. Ten or more cytoplasmic mucin inclusions in a tissue microarray core were seen in 51%, 48% and 31% of the 416 adenocarcinomas and 3%, 4% and 0.5% of the 194 squamous cell carcinomas with PASD, ABPAS and mucicarmine, respectively. Diagnostic pitfalls, such as entrapped benign epithelium, apoptotic/necrotic cells and glycogen, partly differed for the mucin stains. TTF-1 and napsin A IHC stainings had similar specificity but better sensitivity for adenocarcinoma than the mucin stains, but addition of PASD or ABPAS identified more tumors as adenocarcinomas (n = 8 and n = 10, respectively) than napsin A (n = 1) in cases with solid growth that were negative for TTF-1 and p40. We conclude that PASD and ABPAS have similar diagnostic performance and that these markers are of value in poorly differentiated cases. However, morphology and TTF-1 and p40 IHC staining is sufficient for correct diagnosis in most non-small cell lung cancers.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2019
National Category
Cancer and Oncology Cell and Molecular Biology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-377598 (URN)10.1038/s41598-018-37722-0 (DOI)000457616300207 ()30718697 (PubMedID)
Available from: 2019-02-26 Created: 2019-02-26 Last updated: 2020-01-03Bibliographically approved
La Fleur, L., Falk-Sörqvist, E., Smeds, P., Berglund, A., Sundström, M., Mattsson, J. S., . . . Botling, J. (2019). Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11. Lung Cancer, 130, 50-58
Open this publication in new window or tab >>Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11
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2019 (English)In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 130, p. 50-58Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Non-small cell lung cancer (NSCLC) is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients, as well as significant differences in populations across the world with regard to mutation spectra and mutation frequencies. Here we aim to describe mutational patterns and linked clinical parameters in a population-based NSCLC cohort.

MATERIALS AND METHODS: Using targeted resequencing the mutational status of 82 genes was evaluated in a consecutive Swedish surgical NSCLC cohort, consisting of 352 patient samples from either fresh frozen or formalin fixed paraffin embedded (FFPE) tissues. The panel covers all exons of the 82 genes and utilizes reduced target fragment length and two-strand capture making it compatible with degraded FFPE samples.

RESULTS: We obtained a uniform sequencing coverage and mutation load across the fresh frozen and FFPE samples by adaption of sequencing depth and bioinformatic pipeline, thereby avoiding a technical bias between these two sample types. At large, the mutation frequencies resembled the frequencies seen in other western populations, except for a high frequency of KRAS hotspot mutations (43%) in adenocarcinoma patients. Worse overall survival was observed for adenocarcinoma patients with a mutation in either TP53, STK11 or SMARCA4. In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration. Similar results were seen in the analysis of publicly available data from the cBioPortal. In squamous cell carcinoma a worse prognosis could be observed for patients with MLL2 mutations, while CSMD3 mutations were linked to a better prognosis.

CONCLUSION: Here we have evaluated the mutational status of a NSCLC cohort. We could not confirm any survival impact of isolated driver mutations. Instead, concurrent mutations in TP53 and STK11 were shown to confer poor survival in the KRAS-positive adenocarcinoma subgroup.

Keywords
KRAS, Mutation patterns, Non-small cell lung cancer, STK11, TP53, Targeted resequencing
National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-380587 (URN)10.1016/j.lungcan.2019.01.003 (DOI)000463276900008 ()30885352 (PubMedID)
Funder
Swedish Cancer Society, 2013/711Swedish Cancer Society, 2016/827
Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2020-01-03Bibliographically approved
Edlund, K., Madjar, K., Mattsson, J. S., Djureinovic, D., Lindskog, C., Brunnström, H., . . . Hengstler, J. G. (2019). Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC. Journal of Thoracic Oncology, 14(4), 628-640, Article ID S1556-0864(19)30009-7.
Open this publication in new window or tab >>Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
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2019 (English)In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 14, no 4, p. 628-640, article id S1556-0864(19)30009-7Article in journal (Refereed) Published
Abstract [en]

Introduction: Infiltration of T and B/plasma cells has been linked to NSCLC prognosis, but this has not been thoroughly investigated in relation to the expression of programmed death ligand 1 (PD-L1). Here, we determine the association of lymphocytes and PD-L1 with overall survival (OS) in two retrospective cohorts of operated NSCLC patients who were not treated with checkpoint inhibitors targeting the programmed death 1/PD-L1 axis. Moreover, we evaluate how PD-L1 positivity and clinicopathologic factors affect the prognostic association of lymphocytes.

Methods: Cluster of differentiation (CD) 3 (CD3)-, CD8-, CD4-, forkhead box P3 (FOXP3)-, CD20-, CD79A-, and immunoglobulin kappa constant (IGKC)-positive immune cells, and tumor PD-L1 positivity, were determined by immunohistochemistry on tissue microarrays (n = 705). Affymetrix data was analyzed for a patient subset, and supplemented with publicly available transcriptomics data (N = 1724). Associations with OS were assessed by Kaplan-Meier plots and uni- and multivariate Cox regression.

Results: Higher levels of T and B plasma cells were associated with longer OS (p = 0.004 and p < 0.001, for CD8 and IGKC, respectively). Highly proliferative tumors with few lymphocytes had the worst outcome. No association of PD-L1 positivity with OS was observed in a nonstratified patient population; however, a significant association with shorter OS was observed in never-smokers (p = 0.009 and p = 0.002, 5% and 50% cutoff). Lymphocyte infiltration was not associated with OS in PD-L1–positive tumors (50% cutoff). The prognostic association of lymphocyte infiltration also depended on the patients’ smoking history and histologic subtype.

Conclusions: Proliferation, PD-L1 status, smoking history, and histology should be considered if lymphocyte infiltration is to be used as a prognostic biomarker.

Keywords
Adenocarcinoma, Ki67, Lymphocyte, Prognosis, Squamous cell carcinoma
National Category
Clinical Laboratory Medicine Cell and Molecular Biology
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-380592 (URN)10.1016/j.jtho.2018.12.022 (DOI)000462167700021 ()30639618 (PubMedID)
Funder
Swedish Cancer Society, 15 0831
Available from: 2019-03-29 Created: 2019-03-29 Last updated: 2020-01-03Bibliographically approved
Elfving, H., Mattsson, J. S., Lindskog, C., Backman, M., Menzel, U. & Micke, P. (2019). Programmed Cell Death Ligand 1 Immunohistochemistry: A Concordance Study Between Surgical Specimen, Biopsy, and Tissue Microarray. Clinical Lung Cancer, 20(4), 258-262.e1
Open this publication in new window or tab >>Programmed Cell Death Ligand 1 Immunohistochemistry: A Concordance Study Between Surgical Specimen, Biopsy, and Tissue Microarray
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2019 (English)In: Clinical Lung Cancer, ISSN 1525-7304, E-ISSN 1938-0690, Vol. 20, no 4, p. 258-262.e1Article in journal (Refereed) Published
Abstract [en]

Programmed cell death ligand 1 (PD-L1) expression within the same lung cancer tissue is variable. In this study we evaluated if the PD-L1 expression on small biopsy specimens represent the PD-L1 status of the corresponding resection specimen. Our results indicate a relative good agreement between biopsy and surgical specimens, with a discordance in approximately 10% of the cases. Background: The immunohistochemical analysis of programmed cell death ligand 1 (PD-L1) expression in tumor tissue of non-small-cell lung cancer patients has now been integrated in the diagnostic workup. Analysis is commonly done on small tissue biopsy samples representing a minimal fraction of the whole tumor. The aim of the study was to evaluate the correlation of PD-L1 expression on biopsy specimens with corresponding resection specimens. Materials and Methods: In total, 58 consecutive cases with preoperative biopsy and resected tumor specimens were selected. From each resection specimen 2 tumor cores were compiled into a tissue microarray (TMA). Immunohistochemical staining with the antibody SP263 was performed on biopsy specimens, resection specimens (whole sections), as well as on the TMA. Results: The proportion of PD-L1-positive stainings were comparable between the resection specimens (48% and 19%), the biopsies (43% and 17%), and the TMAs (47% and 14%), using cutoffs of 1% and 50%, respectively (P > .39 all comparisons). When the resection specimens were considered as reference, PD-L1 status differed in 16%/5% for biopsies and in 9%/9% for TMAs (1%/50% cutoff). The sensitivity of the biopsy analysis was 79%/82% and the specificity was 90%/98% at the 1%/50% cutoff. The Cohens kappa value for the agreement between biopsy and tumor. was 0.70 at the 1% cutoff and 0.83 at the 50% cutoff. Conclusion: The results indicate a moderate concordance between the analysis of biopsy and whole tumor tissue, resulting in misclassification of samples in particular when the lower 1% cutoff was used. Clinicians should be aware of this uncertainty when interpreting PD-L1 reports for treatment decisions.

Keywords
Checkpoint inhibitors, Nivolumab, PD-1, PD-L1, Pembrolizumab
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-390976 (URN)10.1016/j.cllc.2019.02.012 (DOI)000475296800018 ()30926355 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-08-16 Created: 2019-08-16 Last updated: 2020-01-03Bibliographically approved
Horie, M., Miyashita, N., Mattsson, J. S., Mikami, Y., Sandelin, M., Brunnstrom, H., . . . Saito, A. (2018). An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer. Journal of Pathology, 246(2), 154-165
Open this publication in new window or tab >>An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer
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2018 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 246, no 2, p. 154-165Article in journal (Refereed) Published
Abstract [en]

Small cell lung cancer (SCLC) is a neuroendocrine tumour that exhibits rapid growth and metastatic spread. Although SCLC represents a prototypically undifferentiated cancer type, thyroid transcription factor-1 (TTF-1, gene symbol NKX2-1), a master regulator for pulmonary epithelial cell differentiation and lung morphogenesis, is strongly upregulated in this aggressive cancer type. The aim of this study was to evaluate a functional role for TTF-1 in SCLC. We demonstrated that achaete-scute complex homolog 1 (ASCL1), an essential transcription factor for neuroendocrine differentiation, positively regulated TTF-1 in SCLC cell lines. Subsequently, we described genes and microRNAs (miRNAs) that were possibly controlled by TTF-1 and identified nuclear factor IB (NFIB), a recently characterised driver of SCLC progression, as a transcriptional target of TTF-1. Our findings shine light on a regulatory axis in SCLC consisting of ASCL1/TTF-1/NFIB that potentially contributes to the tumourigenesis of SCLC.

Keywords
SCLC, ASCL1, TTF-1, NFIB, neuroendocrine differentiation
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-366945 (URN)10.1002/path.5109 (DOI)000445203500004 ()29876935 (PubMedID)
Available from: 2018-11-28 Created: 2018-11-28 Last updated: 2019-03-29Bibliographically approved
Vidarsdottir, H., Tran, L., Nodin, B., Jirström, K., Planck, M., Mattsson, J. S., . . . Brunnström, H. (2018). Comparison of Three Different TTF-1 Clones in Resected Primary Lung Cancer and Epithelial Pulmonary Metastase. American Journal of Clinical Pathology, 150(6), 533-544
Open this publication in new window or tab >>Comparison of Three Different TTF-1 Clones in Resected Primary Lung Cancer and Epithelial Pulmonary Metastase
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2018 (English)In: American Journal of Clinical Pathology, ISSN 0002-9173, E-ISSN 1943-7722, Vol. 150, no 6, p. 533-544Article in journal (Refereed) Published
Abstract [en]

Objectives: Immunohistochemical staining against thyroid transcription factor 1 (TTF-1) is often used to distinguish lung adenocarcinoma from squamous cell carcinoma and pulmonary metastasis.

Methods: TTF-1 expression was examined using the antibody clones 8G7G3/1, SPT24, and SP141 on tissue microarrays from 665 cases of resected lung cancers and 428 pulmonary metastases.

Results: Most lung adenocarcinomas, 89%, 93%, and 93%, were positive with TTF-1 clones 8G7G3/1, SPT24, and SP141, respectively. The corresponding figures for lung squamous cell carcinomas were 0%, 6%, and 8%. In total, five (2%), 19 (7%), and 21 (8%) of the pulmonary metastases from colorectal adenocarcinomas were positive with clones 8G7G3/1, SPT24, and SP141, respectively. Other TTF-1-positive pulmonary metastases (n = 8) were thyroid, urothelial, pancreatic, small bowel, and cervix carcinomas.

Conclusions: TTF-1 expression in lung cancer and pulmonary metastases differs between clones, with 8G7G3/1 being more specific but less sensitive compared with SPT24 and SP141.

National Category
Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-372014 (URN)10.1093/ajcp/aqy083 (DOI)000456564300008 ()30169783 (PubMedID)
Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-03-29Bibliographically approved
Gulyas, M., Mattsson, J. S., Lindgren, A., Ek, L., Lamberg Lundström, K., Behndig, A., . . . Bergman, B. (2018). COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer.. Acta Oncologica, 57(2), 244-250
Open this publication in new window or tab >>COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer.
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 244-250Article in journal (Refereed) Published
Abstract [en]

Aim: Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyze COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition.

Methods: In a multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b.i.d.) or placebo up to one year in addition to a two-drug platinum-based chemotherapy combination. In a subset of 122 patients, archived tumor tissue was available for immunohistochemical analysis of COX-2 expression in tumor and stromal cells. For each compartment, COX-2 expression was graded as high or low, based on a product score of extension and intensity of positively stained cells.

Results: An updated analysis of all 316 patients included in the original trial, and of the 122 patients with available tumor tissue, showed no survival differences between the celecoxib and placebo arms (HR 1.01; 95% CI 0.81–1.27 and HR 1.12; 95% CI 0.78–1.61, respectively). High COX-2 scores in tumor (n = 71) or stromal cells (n = 55) was not associated with a superior survival outcome with celecoxib vs. placebo (HR =0.96, 95% CI 0.60–1.54; and HR =1.51; 95% CI 0.86–2.66), and no significant interaction effect between COX-2 score in tumor or stromal cells and celecoxib effect on survival was detected (p = .48 and .25, respectively).

Conclusions: In this subgroup analysis of patients with advanced NSCLC treated within the context of a randomized trial, we could not detect any interaction effect of COX-2 expression in tumor or stromal cells and the outcome of celecoxib treatment in addition to standard chemotherapy.

National Category
Clinical Medicine Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-343645 (URN)10.1080/0284186X.2017.1400685 (DOI)000423473200011 ()29140138 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2019-04-02Bibliographically approved
La Fleur, L., Boura, V. F., Alexeyenko, A., Berglund, A., Ponten, V., Mattsson, J. S., . . . Botling, J. (2018). Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer. International Journal of Cancer, 143(7), 1741-1752
Open this publication in new window or tab >>Expression of scavenger receptor MARCO defines a targetable tumor-associated macrophage subset in non-small cell lung cancer
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 7, p. 1741-1752Article in journal (Refereed) Published
Abstract [en]

Tumor-associated macrophages (TAMs) are attractive targets for immunotherapy. Recently, studies in animal models showed that treatment with an anti-TAM antibody directed against the scavenger receptor MARCO resulted in suppression of tumor growth and metastatic dissemination. Here we investigated the expression of MARCO in relation to other macrophage markers and immune pathways in a non-small cell lung cancer (NSCLC) cohort (n=352). MARCO, CD68, CD163, MSR1 and programmed death ligand-1 (PD-L1) were analyzed by immunohistochemistry and immunofluorescence, and associations to other immune cells and regulatory pathways were studied in a subset of cases (n=199) with available RNA-seq data. We observed a large variation in macrophage density between cases and a strong correlation between CD68 and CD163, suggesting that the majority of TAMs present in NSCLC exhibit a protumor phenotype. Correlation to clinical data only showed a weak trend toward worse survival for patients with high macrophage infiltration. Interestingly, MARCO was expressed on a distinct subpopulation of TAMs, which tended to aggregate in close proximity to tumor cell nests. On the transcriptomic level, we found a positive association between MARCO gene expression and general immune response pathways including strong links to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules. Indeed, a higher macrophage infiltration was seen in tumors expressing PD-L1, and macrophages residing within tumor cell nests co-expressed MARCO and PD-L1. Thus, MARCO is a potential new immune target for anti-TAM treatment in a subset of NSCLC patients, possibly in combination with available immune checkpoint inhibitors.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
lung cancer, MARCO, tumor-associated macrophages, immune therapy, PD-L1
National Category
Cancer and Oncology Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-364230 (URN)10.1002/ijc.31545 (DOI)000443392100020 ()29667169 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-10-24 Created: 2018-10-24 Last updated: 2019-08-20Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5294-7808

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