Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

被引:16
作者
Wheat, Rachel [1 ]
Roberts, Claudia [1 ,2 ]
Waterboer, Tim [3 ]
Steele, Jane [4 ]
Marsden, Jerry [2 ]
Steven, Neil [1 ,2 ]
Blackbourn, David [5 ]
机构
[1] Univ Birmingham, Coll Med & Dent Sci, Sch Canc Sci & CR UK Ctr Canc Res, Birmingham B15 2TT, W Midlands, England
[2] Univ Hosp Birmingham, New Queen Elizabeth Hosp Birmingham, NHS Fdn Trust, Mindelsohn Way, Birmingham B15 2WB, W Midlands, England
[3] DKFZ German Canc Res Ctr, Infect & Canc Program, D-69120 Heidelberg, Germany
[4] Univ Birmingham, Coll Med & Dent Sci, Human Biomat Resource Ctr, Birmingham B15 2TT, W Midlands, England
[5] Univ Surrey, Fac Hlth & Med Sci, Dept Microbial & Cellular Sci, Guildford GU2 7XH, Surrey, England
关键词
Merkel cell carcinoma; lymphocyte; polyomavirus; immunohistochemistry; confocal microscopy;
D O I
10.3390/cancers6021047
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Merkel cell carcinoma (MCC) is an aggressive poorly differentiated neuroendocrine cutaneous carcinoma associated with older age, immunodeficiency and Merkel cell polyomavirus (MCPyV) integrated within malignant cells. The presence of intra-tumoural CD8+ lymphocytes reportedly predicts better MCC-specific survival. In this study, the distribution of inflammatory cells and properties of CD8+ T lymphocytes within 20 primary MCC specimens were characterised using immunohistochemistry and multicolour immunofluorescent staining coupled to confocal microscopy. CD8+ cells and CD68+ macrophages were identified in 19/20 primary MCC. CD20+ B cells were present in 5/10, CD4+ cells in 10/10 and FoxP3+ cells in 7/10 specimens. Only two specimens had almost no inflammatory cells. Within specimens, inflammatory cells followed the same patchy distribution, focused at the edge of sheets and nodules and, in some cases, more intense in trabecular areas. CD8+ cells were outside vessels on the edge of tumour. Those few within malignant sheets typically lined up in fine septa not contacting MCC cells expressing MCPyV large T antigen. The homeostatic chemokine CXCL12 was expressed outside malignant nodules whereas its receptor CXCR4 was identified within tumour but not on CD8+ cells. CD8+ cells lacked CXCR3 and granzyme B expression irrespective of location within stroma versus malignant nodules or of the intensity of the intra-tumoural infiltrate. In summary, diverse inflammatory cells were organised around the margin of malignant deposits suggesting response to aberrant signaling, but were unable to penetrate the tumour microenvironment itself to enable an immune response against malignant cells or their polyomavirus.
引用
收藏
页码:1047 / 1064
页数:18
相关论文
共 42 条
[1]   Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study [J].
Albores-Saavedra, Jorge ;
Batich, Kristen ;
Chable-Montero, Freddy ;
Sagy, Noa ;
Schwartz, Arnold M. ;
Henson, Donald Earl .
JOURNAL OF CUTANEOUS PATHOLOGY, 2010, 37 (01) :20-27
[2]   Merkel cell carcinoma: Prognosis and treatment of patients from a single institution [J].
Allen, PJ ;
Bowne, WB ;
Jaques, DP ;
Brennan, MF ;
Busam, K ;
Coit, DG .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (10) :2300-2309
[3]   Merkel cell carcinoma: Critical review with guidelines for multidisciplinary management [J].
Bichakjian, Christopher K. ;
Lowe, Lori ;
Lao, Christopher D. ;
Sandler, Howard M. ;
Bradford, Carol R. ;
Johnson, Timothy M. ;
Wong, Sandra L. .
CANCER, 2007, 110 (01) :1-12
[4]   A chemokine-dependent stromal induction mechanism for aberrant lymphocyte accumulation and compromised lymphatic return in rheumatoid arthritis [J].
Burman, A ;
Haworth, O ;
Hardie, DL ;
Amft, EN ;
Siewert, C ;
Jackson, DG ;
Salmon, M ;
Buckley, CD .
JOURNAL OF IMMUNOLOGY, 2005, 174 (03) :1693-1700
[5]   Regarding Complete Spontaneous Regression of Merkel Cell Carcinoma [J].
Connelly, Tom .
DERMATOLOGIC SURGERY, 2009, 35 (04) :721-721
[6]   Granzymes in cancer and immunity [J].
Cullen, S. P. ;
Brunet, M. ;
Martin, S. J. .
CELL DEATH AND DIFFERENTIATION, 2010, 17 (04) :616-623
[7]   Merkel cell carcinoma and HIV infection [J].
Engels, EA ;
Frisch, M ;
Goedert, JJ ;
Biggar, RJ ;
Miller, RW .
LANCET, 2002, 359 (9305) :497-498
[8]   A quarter century of granzymes [J].
Ewen, C. L. ;
Kane, K. P. ;
Bleackley, R. C. .
CELL DEATH AND DIFFERENTIATION, 2012, 19 (01) :28-35
[9]   Memory T cells constitute a subset of the human CD8+CD45RA+ pool with distinct phenotypic and migratory characteristics [J].
Faint, JM ;
Annels, NE ;
Curnow, SJ ;
Shields, P ;
Pilling, D ;
Hislop, AD ;
Wu, LJ ;
Akbar, AN ;
Buckley, CD ;
Moss, PAH ;
Adams, DH ;
Rickinson, AB ;
Salmon, M .
JOURNAL OF IMMUNOLOGY, 2001, 167 (01) :212-220
[10]   Targeting CXCL12 from FAP-expressing carcinomaassociated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer [J].
Feig, Christine ;
Jones, James O. ;
Kraman, Matthew ;
Wells, Richard J. B. ;
Deonarine, Andrew ;
Chan, Derek S. ;
Connell, Claire M. ;
Roberts, Edward W. ;
Zhao, Qi ;
Caballero, Otavia L. ;
Teichmann, Sarah A. ;
Janowitz, Tobias ;
Jodrell, Duncan I. ;
Tuveson, David A. ;
Fearon, Douglas T. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (50) :20212-20217