Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma.
BACKGROUND
Tumour infiltrating lymphocytes (TIL) are generally considered to represent a host immune response directed against tumour antigens. TIL are also increasingly recognised as possible prognostic parameters. However, the effects observed are variable indicating that results cannot be extrapolated from type of tumour to another. Moreover, it has been suggested that primary solid tumours may be ignored by the immune system and that a meaningful immune response is only mounted in regional lymph nodes.


METHODS
We have examined the local distribution of immune cells in tumour-related compartments in head and neck squamous cell carcinomas (HNSCC). In a second step, the prognostic impact of these cells on disease-free survival (DFS) was analysed. A total of 198 tissue cores from 33 patients were evaluated using tissue mircroarray technique and immunohistochemistry. Tumour-infiltrating immune cells were identified using antibodies specific for CD3, CD8, GranzymeB, FoxP3, CD20 and CD68 and quantified using an image analysis system.


RESULTS
We demonstrate a relative expansion of FoxP3+ regulatory T-cells (Treg) and of cytotoxic T-cells among tumour infiltrating T-cells. We also show that intratumoural CD20+ B-cells are significantly more frequent in metastatic deposits than in primary tumours. Furthermore, we observed a reduced number of peritumoural CD8+ T-cells in metastatic lymph nodes as compared to univolved regional nodes suggesting a local down-modulation of cellular immunity. All other immune cells did not show significant alterations in distribution. We did not observe an association of tumour infiltrating immune cells at the primary site with outcome. However, increased numbers of intraepithelial CD8+ TIL in metastatic tumours as well as large numbers of peritumoural B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect on patient outcome was observed for Treg in any compartment.


CONCLUSIONS
Our results suggest that alterations in lymphocyte distribution in regional lymph nodes rather than at the primary tumour site may be relevant for patient prognosis. Moreover, we demonstrate that in addition to cellular immunity humoral immune responses may be clinically relevant in anti-tumour immunity.
Pretscher
Dominik
D
Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nuremberg, Germany. dpretscher@gmx.de
Distel
Luitpold V
LV
Grabenbauer
Gerhard G
GG
Wittlinger
Michael
M
Buettner
Maike
M
Niedobitek
Gerald
G
D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008207:Lymphatic Metastasis; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010610:Pharyngeal Neoplasms / Q000276:immunology* / Q000473:pathology
D018951:Antigens, CD20; D018122:B7-1 Antigen
Clin Cancer Res. 2007 Feb 1;13(3):902-11
17289884
Ear Nose Throat J. 2007 Aug;86(8):506-11
17915676
Clin Cancer Res. 2000 May;6(5):1875-81
10815910
Prostate. 2006 Dec 1;66(16):1710-20
16955408
Cancer Res. 1998 Aug 15;58(16):3491-4
9721846
Blood. 2006 Nov 1;108(9):2957-64
16825494
PLoS Med. 2005 Sep;2(9):e284
16124834
J Surg Res. 2005 Mar;124(1):151-7
15734494
Clin Cancer Res. 2006 Jun 1;12(11 Pt 1):3355-60
16740757
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2233-8
10051624
Cancer Res. 2009 Mar 1;69(5):2000-9
19244125
Cancer Immunol Immunother. 2006 Sep;55(9):1064-71
16328385
Cancer. 1996 Oct 15;78(8):1677-85
8859180
Cancer Res. 2006 Sep 15;66(18):9281-9
16982773
J Natl Cancer Inst. 2008 Mar 19;100(6):407-20
18334711
J Clin Oncol. 2005 Dec 10;23(35):8932-41
16219933
Oncogene. 2008 Oct 6;27(45):5904-12
18836471
Cancer Res. 2003 Jun 15;63(12):3275-80
12810659
Clin Immunol. 2002 Jan;102(1):37-47
11781066
Clin Cancer Res. 2006 Jan 15;12(2):465-72
16428488
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18538-43
16344461
Nat Med. 2004 Sep;10(9):942-9
15322536
J Natl Cancer Inst. 1987 Mar;78(3):399-405
3469453
Lancet. 2001 Feb 17;357(9255):539-45
11229684
Clin Cancer Res. 2005 Feb 15;11(4):1467-73
15746048
Int J Cancer. 2001 Jul 1;93(1):1-5
11391613
Int J Cancer. 2008 Nov 15;123(10):2354-61
18729197
Cancer Res. 2003 Apr 1;63(7):1555-9
12670904
Cancer Immun. 2008 Dec 04;8:16
19053167
Curr Oncol Rep. 2006 Mar;8(2):130-9
16507223
Am J Surg Pathol. 2005 Feb;29(2):167-78
15644773
Cancer Res. 2008 Jul 1;68(13):5405-13
18593943