Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer
详细信息 查看全文
- 作者：Elena García-Martínez (1)
Ginés Luengo Gil (1)
Asunción Chaves Benito (2)
Enrique González-Billalabeitia (1)
María Angeles Vicente Conesa (1)
Teresa García García (1)
Elisa García-Garre (1)
Vicente Vicente (1) (3)
Francisco Ayala de la Pe?a (1) - 刊名：Breast Cancer Research
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：16
- 期：6
- 全文大小：1,646 KB
- 参考文献：1. Chen AM, Meric-Bernstam F, Hunt KK, Thames HD, Oswald MJ, Outlaw ED, Strom EA, McNeese MD, Kuerer HM, Ross MI, Singletary SE, Ames FC, Feig BW, Sahin AA, Perkins GH, Schechter NR, Hortobagyi GN, Buchholz TA: Breast conservation after neoadjuvant chemotherapy: the MD Anderson cancer center experience. / J Clin Oncol 2004, 22:2303-312. CrossRef
2. Beriwal S, Schwartz GF, Komarnicky L, Garcia-Young JA: Breast-conserving therapy after neoadjuvant chemotherapy: long-term results. / Breast J 2002, 12:159-64. CrossRef
3. Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, Denkert C, Eiermann W, Gnant M, Harris JR, Karn T, Liedtke C, Mauri D, Rouzier R, Ruckhaeberle E, Semiglazov V, Symmans WF, Tutt A, Pusztai L: Recommendations from an international consensus conference on the current status and future of neoadjuvant systemic therapy in primary breast cancer. / Ann Surg Oncol 2012, 19:1508-516. CrossRef
4. 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, / et al: Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. / Lancet 2014, 384:164-72. CrossRef
5. Bear HD, Anderson S, Smith RE, Geyer CE, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N: Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical Adjuvant Breast and Bowel Project Protocol B-27. / J Clin Oncol 2006, 24:2019-027. CrossRef
6. Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, Margolese RG, Hoehn JL, Vogel VG, Dakhil SR, Tamkus D, King KM, Pajon ER, Wright MJ, Robert J, Paik S, Mamounas EP, Wolmark N: Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. / J Clin Oncol 2008, 26:778-85. CrossRef
7. Senovilla L, Vitale I, Martins I, Tailler M, Pailleret C, Michaud M, Galluzzi L, Adjemian S, Kepp O, Niso-Santano M, Shen S, Mari?o G, Criollo A, Boilève A, Job B, Ladoire S, Ghiringhelli F, Sistigu A, Yamazaki T, Rello-Varona S, Locher C, Poirier-Colame V, Talbot M, Valent A, Berardinelli F, Antoccia A, Ciccosanti F, Fimia GM, Piacentini M, Fueyo A, / et al: An immunosurveillance mechanism controls cancer cell ploidy. / Science 2012, 337:1678-684. CrossRef
8. Reiman JM, Kmieciak M, Manjili MH, Knutson KL: Tumor immunoediting and immunosculpting pathways to cancer progression. / Semin Cancer Biol 2007, 17:275-87. CrossRef
9. Zitvogel L, Kepp O, Kroemer G: Immune parameters affecting the efficacy of chemotherapeutic regimens. / Nat Rev Clin Oncol 2011, 8:151-60. CrossRef
10. Andre F, Dieci MV, Dubsky P, Sotiriou C, Curigliano G, Denkert C, Loi S: Molecular pathways: involvement of immune pathways in the therapeutic response and outcome - 作者单位：Elena García-Martínez (1)
Ginés Luengo Gil (1)
Asunción Chaves Benito (2)
Enrique González-Billalabeitia (1)
María Angeles Vicente Conesa (1)
Teresa García García (1)
Elisa García-Garre (1)
Vicente Vicente (1) (3)
Francisco Ayala de la Pe?a (1)
1. Department of Hematology and Medical Oncology, University Hospital Morales Meseguer, Murcia, Spain
2. Department of Pathology, University Hospital Morales Meseguer, Murcia, Spain
3. Centro Regional de Hemodonación, Murcia, Spain - ISSN：1465-5411
文摘
Introduction Tumor microenvironment immunity is associated with breast cancer outcome. A high lymphocytic infiltration has been associated with response to neoadjuvant chemotherapy, but the contribution to response and prognosis of immune cell subpopulations profiles in both pre-treated and post-treatment residual tumor is still unclear. Methods We analyzed pre- and post-treatment tumor-infiltrating immune cells (CD3, CD4, CD8, CD20, CD68, Foxp3) by immunohistochemistry in a series of 121 breast cancer patients homogeneously treated with neoadjuvant chemotherapy. Immune cell profiles were analyzed and correlated with response and survival. Results We identified three tumor-infiltrating immune cell profiles, which were able to predict pathological complete response (pCR) to neoadjuvant chemotherapy (cluster B: 58%, versus clusters A and C: 7%). A higher infiltration by CD4 lymphocytes was the main factor explaining the occurrence of pCR, and this association was validated in six public genomic datasets. A higher chemotherapy effect on lymphocytic infiltration, including an inversion of CD4/CD8 ratio, was associated with pCR and with better prognosis. Analysis of the immune infiltrate in post-chemotherapy residual tumor identified a profile (cluster Y), mainly characterized by high CD3 and CD68 infiltration, with a worse disease free survival. Conclusions Breast cancer immune cell subpopulation profiles, determined by immunohistochemistry-based computerized analysis, identify groups of patients characterized by high response (in the pre-treatment setting) and poor prognosis (in the post-treatment setting). Further understanding of the mechanisms underlying the distribution of immune cells and their changes after chemotherapy may contribute to the development of new immune-targeted therapies for breast cancer.