Skip to main content
Erschienen in:

27.01.2022 | Original Paper

A CD8+ T Cell-Related Genes Expression Signature Predicts Prognosis and the Efficacy of Immunotherapy in Breast Cancer

verfasst von: Lian-hua Lv, Jia-rong Lu, Tao Zhao, Jing-li Liu, Hai-qi Liang

Erschienen in: Journal of Mammary Gland Biology and Neoplasia | Ausgabe 1/2022

Einloggen, um Zugang zu erhalten

Abstract

Immunotherapy has been applied to patients with breast cancer. However, only part of patients benefits from the current immunotherapy. Accurate prediction of individual response to immunotherapy can be beneficial for breast cancer management. CD8+ T cells are the main force of anti-tumor immunity. This study aimed to establish a CD8+ T cell-related gene expression signature for prediction of breast cancer prognostic and immunotherapy efficacy. RNA-seq transcriptomic data was the basics of this research. Weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis established the prognostic signature. We identified 290 CD8+ T cell-related genes in the training set and established a risk-score model based on 8-genes panel (SOCS1, IL10, CAMK4, CXCL13, KIR2DS4, TESPA1, CD70 and ICAM4). Subsequently, univariate Cox regression analysis suggested that high risk-score was a risk factor for breast cancer (HR = 3.1, 95%CI 2.0–4.8, P < 0.001). In tumor microenvironment, high-risk tumors present decreased tumor infiltrating CD8+ T cells and increased M2 macrophages. The low-risk patients may benefit more from immune checkpoint blockade immunotherapy than the high-risk patients. Moreover, breast tumors which sensitive to immune checkpoint inhibitor (ICI) showed higher IL10 expression.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33.CrossRef Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33.CrossRef
2.
Zurück zum Zitat Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.PubMed Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.PubMed
3.
Zurück zum Zitat DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67:439–48.CrossRef DeSantis CE, Ma J, Goding Sauer A, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67:439–48.CrossRef
4.
Zurück zum Zitat Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer Nat Rev Dis Primers. 2019;5:66.CrossRef Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer Nat Rev Dis Primers. 2019;5:66.CrossRef
5.
Zurück zum Zitat Reading JL, Gálvez-Cancino F, Swanton C, Lladser A, Peggs KS, Quezada SA. The function and dysfunction of memory CD8(+) T cells in tumor immunity. Immunol Rev. 2018;283:194–212.CrossRef Reading JL, Gálvez-Cancino F, Swanton C, Lladser A, Peggs KS, Quezada SA. The function and dysfunction of memory CD8(+) T cells in tumor immunity. Immunol Rev. 2018;283:194–212.CrossRef
6.
Zurück zum Zitat Baxevanis CN, Fortis SP, Perez SA. The balance between breast cancer and the immune system: Challenges for prognosis and clinical benefit from immunotherapies. Semin Cancer Biol. 2019. Baxevanis CN, Fortis SP, Perez SA. The balance between breast cancer and the immune system: Challenges for prognosis and clinical benefit from immunotherapies. Semin Cancer Biol. 2019.
7.
Zurück zum Zitat Ali HR, Provenzano E, Dawson SJ, Blows FM, Liu B, Shah M, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol. 2014;25:1536–43.CrossRef Ali HR, Provenzano E, Dawson SJ, Blows FM, Liu B, Shah M, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol. 2014;25:1536–43.CrossRef
8.
Zurück zum Zitat van der Leun AM, Thommen DS, Schumacher TN. CD8(+) T cell states in human cancer: insights from single-cell analysis. Nat Rev Cancer. 2020;20:218–32.CrossRef van der Leun AM, Thommen DS, Schumacher TN. CD8(+) T cell states in human cancer: insights from single-cell analysis. Nat Rev Cancer. 2020;20:218–32.CrossRef
9.
Zurück zum Zitat Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565–94.CrossRef Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565–94.CrossRef
10.
Zurück zum Zitat Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350–5.CrossRef Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350–5.CrossRef
11.
Zurück zum Zitat Catacchio I, Silvestris N, Scarpi E, Schirosi L, Scattone A, Mangia A. Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients. Transl Oncol. 2019;12:585–95.CrossRef Catacchio I, Silvestris N, Scarpi E, Schirosi L, Scattone A, Mangia A. Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients. Transl Oncol. 2019;12:585–95.CrossRef
12.
Zurück zum Zitat Xie P, Ma Y, Yu S, An R, He J, Zhang H. Development of an Immune-Related Prognostic Signature in Breast Cancer. Front Genet. 2019;10:1390.CrossRef Xie P, Ma Y, Yu S, An R, He J, Zhang H. Development of an Immune-Related Prognostic Signature in Breast Cancer. Front Genet. 2019;10:1390.CrossRef
13.
Zurück zum Zitat Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, et al. The human genome browser at UCSC. Genome Res. 2002;12:996–1006.CrossRef Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, et al. The human genome browser at UCSC. Genome Res. 2002;12:996–1006.CrossRef
14.
Zurück zum Zitat Kao KJ, Chang KM, Hsu HC, Huang AT. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization. BMC Cancer. 2011;11:143.CrossRef Kao KJ, Chang KM, Hsu HC, Huang AT. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization. BMC Cancer. 2011;11:143.CrossRef
15.
Zurück zum Zitat Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, et al. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007;13:3207–14.CrossRef Desmedt C, Piette F, Loi S, Wang Y, Lallemand F, Haibe-Kains B, et al. Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series. Clin Cancer Res. 2007;13:3207–14.CrossRef
16.
Zurück zum Zitat Desmedt C, Di Leo A, de Azambuja E, Larsimont D, Haibe-Kains B, Selleslags J, et al. Multifactorial approach to predicting resistance to anthracyclines. J Clin Oncol. 2011;29:1578–86.CrossRef Desmedt C, Di Leo A, de Azambuja E, Larsimont D, Haibe-Kains B, Selleslags J, et al. Multifactorial approach to predicting resistance to anthracyclines. J Clin Oncol. 2011;29:1578–86.CrossRef
17.
Zurück zum Zitat Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell. 2006;10:529–41.CrossRef Chin K, DeVries S, Fridlyand J, Spellman PT, Roydasgupta R, Kuo WL, et al. Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell. 2006;10:529–41.CrossRef
18.
Zurück zum Zitat Sabatier R, Finetti P, Cervera N, Lambaudie E, Esterni B, Mamessier E, et al. A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Res Treat. 2011;126:407–20.CrossRef Sabatier R, Finetti P, Cervera N, Lambaudie E, Esterni B, Mamessier E, et al. A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Res Treat. 2011;126:407–20.CrossRef
19.
Zurück zum Zitat Hatzis C, Pusztai L, Valero V, Booser DJ, Esserman L, Lluch A, et al. A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. JAMA. 2011;305:1873–81.CrossRef Hatzis C, Pusztai L, Valero V, Booser DJ, Esserman L, Lluch A, et al. A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. JAMA. 2011;305:1873–81.CrossRef
20.
Zurück zum Zitat Filipits M, Rudas M, Jakesz R, Dubsky P, Fitzal F, Singer CF, et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res. 2011;17:6012–20.CrossRef Filipits M, Rudas M, Jakesz R, Dubsky P, Fitzal F, Singer CF, et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res. 2011;17:6012–20.CrossRef
21.
Zurück zum Zitat Chung W, Eum HH, Lee HO, Lee KM, Lee HB, Kim KT, et al. Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer. Nat Commun. 2017;8:15081.CrossRef Chung W, Eum HH, Lee HO, Lee KM, Lee HB, Kim KT, et al. Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer. Nat Commun. 2017;8:15081.CrossRef
22.
Zurück zum Zitat Hollern DP, Xu N, Thennavan A, Glodowski C, Garcia-Recio S, Mott KR, et al. B Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer. Cell. 2019;179:1191-206.e21.CrossRef Hollern DP, Xu N, Thennavan A, Glodowski C, Garcia-Recio S, Mott KR, et al. B Cells and T Follicular Helper Cells Mediate Response to Checkpoint Inhibitors in High Mutation Burden Mouse Models of Breast Cancer. Cell. 2019;179:1191-206.e21.CrossRef
23.
Zurück zum Zitat Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554:544–8.CrossRef Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554:544–8.CrossRef
24.
Zurück zum Zitat Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.CrossRef Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.CrossRef
25.
Zurück zum Zitat Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545–50.CrossRef Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102:15545–50.CrossRef
26.
Zurück zum Zitat Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.CrossRef Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559.CrossRef
27.
Zurück zum Zitat Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–7.CrossRef Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–7.CrossRef
28.
Zurück zum Zitat Charoentong P, Finotello F, Angelova M, Mayer C, Efremova M, Rieder D, et al. Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade. Cell Rep. 2017;18:248–62.CrossRef Charoentong P, Finotello F, Angelova M, Mayer C, Efremova M, Rieder D, et al. Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade. Cell Rep. 2017;18:248–62.CrossRef
29.
Zurück zum Zitat Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67–76.CrossRef Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67–76.CrossRef
30.
Zurück zum Zitat Ilangumaran S, Bobbala D, Ramanathan S. SOCS1: Regulator of T Cells in Autoimmunity and Cancer. Curr Top Microbiol Immunol. 2017;410:159–89.PubMed Ilangumaran S, Bobbala D, Ramanathan S. SOCS1: Regulator of T Cells in Autoimmunity and Cancer. Curr Top Microbiol Immunol. 2017;410:159–89.PubMed
31.
Zurück zum Zitat Deng XX, Jiao YN, Hao HF, Xue D, Bai CC, Han SY. Taraxacum mongolicum extract inhibited malignant phenotype of triple-negative breast cancer cells in tumor-associated macrophages microenvironment through suppressing IL-10 / STAT3 / PD-L1 signaling pathways. J Ethnopharmacol. 2021;274:113978. Deng XX, Jiao YN, Hao HF, Xue D, Bai CC, Han SY. Taraxacum mongolicum extract inhibited malignant phenotype of triple-negative breast cancer cells in tumor-associated macrophages microenvironment through suppressing IL-10 / STAT3 / PD-L1 signaling pathways. J Ethnopharmacol. 2021;274:113978.
32.
Zurück zum Zitat Koga T, Kawakami A. The role of CaMK4 in immune responses. Mod Rheumatol. 2018;28:211–4.CrossRef Koga T, Kawakami A. The role of CaMK4 in immune responses. Mod Rheumatol. 2018;28:211–4.CrossRef
33.
Zurück zum Zitat Hensel O, Burow P, Mages S, Wienke A, Kraya T, Zierz S. Increased Blood Flow Velocity in Middle Cerebral Artery and Headache Upon Ingestion of Ice Water. Front Neurol. 2019;10:677.CrossRef Hensel O, Burow P, Mages S, Wienke A, Kraya T, Zierz S. Increased Blood Flow Velocity in Middle Cerebral Artery and Headache Upon Ingestion of Ice Water. Front Neurol. 2019;10:677.CrossRef
34.
Zurück zum Zitat Ihanus E, Uotila LM, Toivanen A, Varis M, Gahmberg CG. Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4. Blood. 2007;109:802–10.CrossRef Ihanus E, Uotila LM, Toivanen A, Varis M, Gahmberg CG. Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4. Blood. 2007;109:802–10.CrossRef
35.
Zurück zum Zitat Kamarudin AN, Cox T, Kolamunnage-Dona R. Time-dependent ROC curve analysis in medical research: current methods and applications. BMC Med Res Methodol. 2017;17:53.CrossRef Kamarudin AN, Cox T, Kolamunnage-Dona R. Time-dependent ROC curve analysis in medical research: current methods and applications. BMC Med Res Methodol. 2017;17:53.CrossRef
36.
Zurück zum Zitat Taube JM, Galon J, Sholl LM, Rodig SJ, Cottrell TR, Giraldo NA, et al. Implications of the tumor immune microenvironment for staging and therapeutics. Mod Pathol. 2018;31:214–34.CrossRef Taube JM, Galon J, Sholl LM, Rodig SJ, Cottrell TR, Giraldo NA, et al. Implications of the tumor immune microenvironment for staging and therapeutics. Mod Pathol. 2018;31:214–34.CrossRef
37.
Zurück zum Zitat Hao D, Liu J, Chen M, Li J, Wang L, Li X, et al. Immunogenomic Analyses of Advanced Serous Ovarian Cancer Reveal Immune Score is a Strong Prognostic Factor and an Indicator of Chemosensitivity. Clin Cancer Res. 2018;24:3560–71.CrossRef Hao D, Liu J, Chen M, Li J, Wang L, Li X, et al. Immunogenomic Analyses of Advanced Serous Ovarian Cancer Reveal Immune Score is a Strong Prognostic Factor and an Indicator of Chemosensitivity. Clin Cancer Res. 2018;24:3560–71.CrossRef
38.
Zurück zum Zitat Sui S, An X, Xu C, Li Z, Hua Y, Huang G, et al. An immune cell infiltration-based immune score model predicts prognosis and chemotherapy effects in breast cancer. Theranostics. 2020;10:11938–49.CrossRef Sui S, An X, Xu C, Li Z, Hua Y, Huang G, et al. An immune cell infiltration-based immune score model predicts prognosis and chemotherapy effects in breast cancer. Theranostics. 2020;10:11938–49.CrossRef
39.
Zurück zum Zitat Hu FF, Liu CJ, Liu LL, Zhang Q, Guo AY. Expression profile of immune checkpoint genes and their roles in predicting immunotherapy response. Brief Bioinform. 2020. Hu FF, Liu CJ, Liu LL, Zhang Q, Guo AY. Expression profile of immune checkpoint genes and their roles in predicting immunotherapy response. Brief Bioinform. 2020.
40.
Zurück zum Zitat Petroni G, Buqué A, Zitvogel L, Kroemer G, Galluzzi L. Immunomodulation by targeted anticancer agents. Cancer Cell. 2021;39:310–45.CrossRef Petroni G, Buqué A, Zitvogel L, Kroemer G, Galluzzi L. Immunomodulation by targeted anticancer agents. Cancer Cell. 2021;39:310–45.CrossRef
41.
Zurück zum Zitat Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12:253–68.CrossRef Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12:253–68.CrossRef
42.
Zurück zum Zitat Funes SC, Rios M, Escobar-Vera J, Kalergis AM. Implications of macrophage polarization in autoimmunity. Immunology. 2018;154:186–95.CrossRef Funes SC, Rios M, Escobar-Vera J, Kalergis AM. Implications of macrophage polarization in autoimmunity. Immunology. 2018;154:186–95.CrossRef
43.
Zurück zum Zitat Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21:44–59.CrossRef Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21:44–59.CrossRef
Metadaten
Titel
A CD8+ T Cell-Related Genes Expression Signature Predicts Prognosis and the Efficacy of Immunotherapy in Breast Cancer
verfasst von
Lian-hua Lv
Jia-rong Lu
Tao Zhao
Jing-li Liu
Hai-qi Liang
Publikationsdatum
27.01.2022
Verlag
Springer US
Erschienen in
Journal of Mammary Gland Biology and Neoplasia / Ausgabe 1/2022
Print ISSN: 1083-3021
Elektronische ISSN: 1573-7039
DOI
https://doi.org/10.1007/s10911-022-09510-0

Neu im Fachgebiet Onkologie

KI-gestütztes Mammografiescreening überzeugt im Praxistest

Mit dem Einsatz künstlicher Intelligenz lässt sich die Detektionsrate im Mammografiescreening offenbar deutlich steigern. Mehr unnötige Zusatzuntersuchungen sind laut der Studie aus Deutschland nicht zu befürchten.

Welche Krebserkrankungen bei Zöliakie häufiger auftreten

Eine große Kohortenstudie hat den Zusammenhang zwischen Zöliakie und gastrointestinalen Krebserkrankungen und inflammatorischen Krankheiten untersucht. Neben gastrointestinalen Tumoren ist auch ein nicht solider Krebs häufiger.

Adjuvanter PD-L1-Hemmer verhindert Rezidive bei Hochrisiko-Urothelkarzinom

Sind Menschen mit muskelinvasivem Urothelkarzinom für die neoadjuvante platinbasierte Therapie nicht geeignet oder sprechen sie darauf nicht gut an, ist Pembrolizumab eine adjuvante Alternative: Die krankheitsfreie Lebenszeit wird dadurch mehr als verdoppelt.

Duale Checkpointhemmung gegen Melanome verlängert langfristig das Leben

Im Vergleich zu den Überlebenschancen vor der Einführung von Immuncheckpointhemmern (ICI) ist der Fortschritt durch eine ICI-Kombination mit unterschiedlichen Tagets bei fortgeschrittenem Melanom erstaunlich. Das belegen die finalen Ergebnisse der CheckMate-067-Studie und geben Betroffenen "Hoffnung auf Heilung".

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.