nach oben

Erschienen in:

01.06.2018 | Preclinical study

The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome

verfasst von: H. Arias-Pulido, A. Cimino-Mathews, N. Chaher, C. Qualls, N. Joste, C. Colpaert, J. D. Marotti, M. Foisey, E. R. Prossnitz, L. A. Emens, S. Fiering

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The purpose of the study was to evaluate protein expression of PD-L1 and CD20 as prognostic biomarkers of patient outcome in inflammatory breast cancer (IBC) samples.

Methods

PD-L1 and CD20 protein expression was measured by immunohistochemistry in 221 pretreatment IBC biopsies. PD-L1 was assessed in tumor cells (PD-L1⁺ tumor cells) and tumor stromal infiltrating lymphocytes (PD-L1⁺ TILs); CD20 was scored in tumor-infiltrating B cells. Kaplan–Meier curves and Cox proportional hazard models were used for survival analysis.

Results

PD-L1⁺ tumor cells, PD-L1⁺ TILs, and CD20⁺ TILs were found in 8%, 66%, and 62% of IBC, respectively. PD-L1⁺ tumor cells strongly correlated with high TILs, pathological complete response (pCR), CD20⁺ TILs, but marginally with breast cancer-specific survival (BCSS, P = 0.057). PD-L1⁺ TILs strongly correlated with high TILs, CD20⁺ TILs, and longer disease-free survival (DFS) in all IBC and in triple-negative (TN) IBC (P < 0.035). IBC and TN IBC patients with tumors containing both CD20⁺ TILs and PD-L1⁺ TILs (CD20⁺TILs/PD-L1⁺TILs) showed longer DFS and improved BCSS (P < 0.002) than patients lacking both, or those with either CD20⁺ TILs or PD-L1⁺ TILs alone. In multivariate analyses, CD20⁺TILs/PD-L1⁺TILs status was an independent prognostic factor for DFS in IBC (hazard ratio (HR): 0.53, 95% CI 0.37–0.77) and TN IBC (HR: 0.39 95% CI 0.17–0.88), and for BCSS in IBC (HR: 0.60 95% CI 0.43–0.85) and TN IBC (HR: 0.38 95% CI 0.17–0.83).

Conclusion

CD20⁺TILs/PD-L1⁺TILs status represents an independent favorable prognostic factor in IBC and TN IBC, suggesting a critical role for B cells in antitumor immune responses. Anti-PD-1/PD-L1 and B cell-activating immunotherapies should be explored in these settings.

Nur mit Berechtigung zugänglich

Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH (2005) Trends in Inflammatory Breast Carcinoma Incidence and Survival: The Surveillance, Epidemiology, and End Results Program at the National Cancer Institute. J Natl Cancer Inst 97(13):966–975. https://doi.org/10.1093/jnci/dji172 CrossRefPubMedPubMedCentral

Dawood S, Lei X, Dent R, Gupta S, Sirohi B, Cortes J, Cristofanilli M, Buchholz T, Gonzalez-Angulo AM (2014) Survival of women with inflammatory breast cancer: a large population-based study. Ann Oncol 25(6):1143–1151. https://doi.org/10.1093/annonc/mdu121 CrossRefPubMedPubMedCentral

Pierga J-Y, Petit T, Delozier T, Ferrero J-M, Campone M, Gligorov J, Lerebours F, Roché H, Bachelot T, Charafe-Jauffret E, Pavlyuk M, Kraemer S, Bidard F-C, Viens P (2012) Neoadjuvant bevacizumab, trastuzumab, and chemotherapy for primary inflammatory HER2-positive breast cancer (BEVERLY-2): an open-label, single-arm phase 2 study. Lancet Oncol 13(4):375–384. https://doi.org/10.1016/S1470-2045(12)70049-9 CrossRefPubMed

Schlichting JA, Soliman AS, Schairer C, Schottenfeld D, Merajver SD (2012) Inflammatory and non-inflammatory breast cancer survival by socioeconomic position in the Surveillance, Epidemiology, and End Results database, 1990–2008. Breast Cancer Res Treat 134(3):1257–1268. https://doi.org/10.1007/s10549-012-2133-2 CrossRefPubMedPubMedCentral

Dawood S, Ueno N, Valero V, Woodward W, Buchholz T, Hortobagyi G, Gonzalez-Angulo A, Cristofanilli M (2011) Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early: a large population-based study. Cancer 117(9):1819–1826CrossRefPubMed

Gonzalez-Angulo AM, Hennessy BT, Broglio K, Meric-Bernstam F, Cristofanilli M, Giordano SH, Buchholz TA, Sahin A, Singletary SE, Buzdar AU, Hortobagyi GN (2007) Trends for Inflammatory Breast Cancer: Is Survival Improving? Oncologist 12(8):904–912. https://doi.org/10.1634/theoncologist.12-8-904 PubMedCrossRef

Herbst RS, Soria J-C, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HEK, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515(7528):563–567. https://doi.org/10.1038/nature14011 CrossRefPubMedPubMedCentral

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer. New Engl J Med 366(26):2443–2454. https://doi.org/10.1056/NEJMoa1200690 CrossRefPubMed

Nanda R, Chow LQM, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L (2016) Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol 34(21):2460–2467. https://doi.org/10.1200/jco.2015.64.8931 CrossRefPubMed

10.

Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med 8(8):793–800CrossRefPubMed

11.

Chen Daniel S, Mellman I (2013) Oncology Meets Immunology: The Cancer-Immunity Cycle. Immunity 39(1):1–10. https://doi.org/10.1016/j.immuni.2013.07.012 CrossRefPubMed

12.

Emens LA (2018) Breast Cancer Immunotherapy: Facts and Hopes. Clin Cancer Res 24(3):511–520. https://doi.org/10.1158/1078-0432.ccr-16-3001 CrossRefPubMed

13.

Muenst S, Schaerli AR, Gao F, Däster S, Trella E, Droeser RA, Muraro MG, Zajac P, Zanetti R, Gillanders WE, Weber WP, Soysal SD (2014) Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 146(1):15–24. https://doi.org/10.1007/s10549-014-2988-5 CrossRefPubMedPubMedCentral

14.

Beckers RK, Selinger CI, Vilain R, Madore J, Wilmott JS, Harvey K, Holliday A, Cooper CL, Robbins E, Gillett D, Kennedy CW, Gluch L, Carmalt H, Mak C, Warrier S, Gee HE, Chan C, McLean A, Walker E, McNeil CM, Beith JM, Swarbrick A, Scolyer RA, O’Toole SA (2016) Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome. Histopathology 69(1):25–34. https://doi.org/10.1111/his.12904 CrossRefPubMed

15.

Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL (2014) In Situ Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas. Clin Cancer Res 20(10):2773–2782. https://doi.org/10.1158/1078-0432.ccr-13-2702 CrossRefPubMed

16.

Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Ali HR, Viens P, Caldas C, Birnbaum D, Bertucci F (2015) Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 6(7):5449–5464CrossRefPubMed

17.

Brown JR, Wimberly H, Lannin DR, Nixon C, Rimm DL, Bossuyt V (2014) Multiplexed Quantitative Analysis of CD3, CD8, and CD20 Predicts Response to Neoadjuvant Chemotherapy in Breast Cancer. Clin Cancer Res 20(23):5995–6005. https://doi.org/10.1158/1078-0432.ccr-14-1622 CrossRefPubMedPubMedCentral

18.

Mahmoud SMA, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AHS, Ellis IO, Green AR (2011) Tumor-Infiltrating CD8 + Lymphocytes Predict Clinical Outcome in Breast Cancer. J Clin Oncol 29(15):1949–1955. https://doi.org/10.1200/jco.2010.30.5037 CrossRefPubMed

19.

Chaher N, Arias-Pulido H, Terki N, Qualls C, Bouzid K, Verschraegen C, Wallace AM, Royce M (2012) Molecular and epidemiological characteristics of inflammatory breast cancer in Algerian patients. Breast Cancer Res Treat 131(2):437–444. https://doi.org/10.1007/s10549-011-1422-5 CrossRefPubMed

20.

Dawood S, Merajver SD, Viens P, Vermeulen PB, Swain SM, Buchholz TA, Dirix LY, Levine PH, Lucci A, Krishnamurthy S, Robertson FM, Woodward WA, Yang WT, Ueno NT, Cristofanilli M (2010) International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol 22:515–523. https://doi.org/10.1093/annonc/mdq345 CrossRefPubMedPubMedCentral

21.

Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. The Lancet 384(9938):164–172. https://doi.org/10.1016/S0140-6736(13)62422-8 CrossRef

22.

Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S (2015) The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 26(2):259–271. https://doi.org/10.1093/annonc/mdu450 CrossRefPubMed

23.

Altman DG, McShane LM, Sauerbrei W, Taube SE (2012) Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration. PLOS Medicine 9(5):e1001216. https://doi.org/10.1371/journal.pmed.1001216 CrossRefPubMedPubMedCentral

24.

Sunshine JC, Nguyen PL, Kaunitz GJ, Cottrell TR, Berry S, Esandrio J, Xu H, Ogurtsova A, Bleich KB, Cornish TC, Lipson EJ, Anders RA, Taube JM (2017) PD-L1 Expression in Melanoma: A Quantitative Immunohistochemical Antibody Comparison. Clin Cancer Res 23(16):4938–4944. https://doi.org/10.1158/1078-0432.ccr-16-1821 CrossRefPubMed

25.

Mahmoud SMA, Lee AHS, Paish EC, Macmillan RD, Ellis IO, Green AR (2012) The prognostic significance of B lymphocytes in invasive carcinoma of the breast. Breast Cancer Res Treat 132(2):545–553. https://doi.org/10.1007/s10549-011-1620-1 CrossRefPubMed

26.

Lachin JB Methods. John Wiley and Sons, NY, pp 272–2852000

27.

Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N, Bracci L, Breckpot K, Brough D, Buqué A, Castro MG, Cirone M, Colombo MI, Cremer I, Demaria S, Dini L, Eliopoulos AG, Faggioni A, Formenti SC, Fučíková J, Gabriele L, Gaipl US, Galon J, Garg A, Ghiringhelli F, Giese NA, Guo ZS, Hemminki A, Herrmann M, Hodge JW, Holdenrieder S, Honeychurch J, Hu H-M, Huang X, Illidge TM, Kono K, Korbelik M, Krysko DV, Loi S, Lowenstein PR, Lugli E, Ma Y, Madeo F, Manfredi AA, Martins I, Mavilio D, Menger L, Merendino N, Michaud M, Mignot G, Mossman KL, Multhoff G, Oehler R, Palombo F, Panaretakis T, Pol J, Proietti E, Ricci J-E, Riganti C, Rovere-Querini P, Rubartelli A, Sistigu A, Smyth MJ, Sonnemann J, Spisek R, Stagg J, Sukkurwala AQ, Tartour E, Thorburn A, Thorne SH, Vandenabeele P, Velotti F, Workenhe ST, Yang H, Zong W-X, Zitvogel L, Kroemer G, Galluzzi L (2014) Consensus guidelines for the detection of immunogenic cell death. OncoImmunology 3(9):e955691. https://doi.org/10.4161/21624011.2014.955691 CrossRefPubMedPubMedCentral

28.

Bertucci F, Finetti P, Colpaert C, Mamessier E, Parizel M, Dirix L, Viens P, Birnbaum D, van Laere S (2015) PDL1 expression in inflammatory breast cancer is frequent and predicts for the pathological response to chemotherapy. Oncotarget 6(15):13506–13519CrossRefPubMedPubMedCentral

29.

He J, Huo L, Ma J, Zhao J, Bassett RL, Sun X, Ueno NT, Lim B, Gong Y (2018) Expression of Programmed Death Ligand 1 (PD-L1) in Posttreatment Primary Inflammatory Breast Cancers and Clinical Implications. Am J Clin Pathol 149(3):253–261. https://doi.org/10.1093/ajcp/aqx162 CrossRefPubMed

30.

Iglesia MD, Vincent BG, Parker JS, Hoadley KA, Carey LA, Perou CM, Serody JS (2014) Prognostic B-cell Signatures Using mRNA-Seq in Patients with Subtype-Specific Breast and Ovarian Cancer. Clin Cancer Res 20(14):3818–3829. https://doi.org/10.1158/1078-0432.ccr-13-3368 CrossRefPubMedPubMedCentral

31.

Pelekanou V, Carvajal-Hausdorf DE, Altan M, Wasserman B, Carvajal-Hausdorf C, Wimberly H, Brown J, Lannin D, Pusztai L, Rimm DL (2017) Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Res 19(1):91. https://doi.org/10.1186/s13058-017-0884-8 CrossRefPubMedPubMedCentral

32.

Nelson BH (2010) CD20 + B Cells: The Other Tumor-Infiltrating Lymphocytes. J Immunol 185(9):4977–4982. https://doi.org/10.4049/jimmunol.1001323 CrossRefPubMed

Titel: The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome
verfasst von: H. Arias-Pulido
A. Cimino-Mathews
N. Chaher
C. Qualls
N. Joste
C. Colpaert
J. D. Marotti
M. Foisey
E. R. Prossnitz
L. A. Emens
S. Fiering
Publikationsdatum: 01.06.2018
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4834-7

Neu im Fachgebiet Onkologie

25.04.2024 | Nierenkarzinom | Nachrichten

Springer Medizin

The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome

Abstract

Purpose

Methods

Results

Conclusion

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

Machine-learning-derived classifier predicts absence of persistent pain after breast cancer surgery with high accuracy

Malignant and borderline phyllodes tumors of the breast: a multicenter study of 362 patients (KROG 16-08)

Real-time, intraoperative detection of residual breast cancer in lumpectomy cavity walls using a novel cathepsin-activated fluorescent imaging system

High expression of long non-coding RNA MALAT1 in breast cancer is associated with poor relapse-free survival

Phase I study of alpelisib (BYL-719) and trastuzumab emtansine (T-DM1) in HER2-positive metastatic breast cancer (MBC) after trastuzumab and taxane therapy

Evolving surgical treatment decisions for male breast cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie