UroToday.com – The present study (1) had two main objectives. First, we wanted to validate a novel computer-based analysis method for the quantification of immune cell density. Second, to understand the impact of androgen-deprivation therapy (ADT) on the density of immune cell populations infiltrating the prostate.

Several publications have highlighted correlations between the density of immune cell infiltrating the prostate and disease progression. (2-7) However these studies arrive at conflicting conclusions regarding the protective or tumor-promoting role of inflammation in prostate cancer. The discrepancies between these studies are most likely caused by varying staining methods (H&E or antibody staining), quantification of immune cell abundance based on small randomly selected fields and different analysis methods (3+ scale or visual cell count).

As such, we felt it was important to tackle all three aspects and to propose a standardized protocol for the quantification of immune cell abundance. We carefully optimized immunohistochemical staining for several immune cell populations: CD3+ and CD8+ T lymphocytes, CD20+ B lymphocytes, CD56+ Natural Killer cells, CD68+ macrophages and FoxP3+ lymphocytes.

Moreover, due to the heterogeneous nature of prostate inflammation, we eliminated the bias of counting immune cells in randomly selected fields by using a whole-slide scanner, which provides a high-resolution image of the entire pathological sample. Finally, by using the Image-ScopeTM software, we were able to precisely quantify the immune cell abundance. The numerical output generated during the density analysis also permitted robust statistical analyses. We believe that this protocol may facilitate the interpretation of results from independent studies thereby shedding some light as to the role of inflammation in prostate cancer progression.

The second objective of this study was to determine the impact of ADT on the immune cell infiltration. Currently, several immunotherapeutic protocols are tested in clinical trials recruiting patients who have received and failed ADT and have developed hormone refractory prostate cancer. However, little is known regarding the immunoregulatory consequences of ADT in these patients. It is thus crucial to understand whether ADT could render patients more or less responsive to immunotherapy. The results presented in this study demonstrate that only T lymphocytes and macrophages are present in increased density in ADT-treated patients. Our data suggest that these two populations may be more sensitive to immunological changes following ADT.

In conclusion, our work demonstrates that a software-based analysis method coupled to a whole-slide image scanner can accurately quantify the density of immune cells infiltrating prostate specimens. Since most patients fail ADT and develop hormone refractory disease, it is conceivable that the increased infiltration of T lymphocytes and macrophages is not protective for prostate cancer patients. As such, this standardized approach could be used to carefully characterize the immune cell phenotype and, for example, determine if the infiltrating macrophages have an immunosuppressive phenotype.

References:

1. Gannon PO, Poisson AO, Delvoye N, Lapointe R, Mes-Masson AM, Saad F. Characterization of the intra-prostatic immune cell infiltration in androgen-deprived prostate cancer patients. J Immunol Methods 2009;348:9-17.
2. Irani J, Goujon JM, Ragni E, et al. High-grade inflammation in prostate cancer as a prognostic factor for biochemical recurrence after radical prostatectomy. Pathologist Multi Center Study Group. Urology 1999;54:467-72.
3. McArdle PA, Canna K, McMillan DC, McNicol AM, Campbell R, Underwood MA. The relationship between T-lymphocyte subset infiltration and survival in patients with prostate cancer. Br J Cancer 2004;91:541-3.
4. Sari A, Serel TA, Candir O, Ozturk A, Kosar A. Mast cell variations in tumour tissue and with histopathological grading in specimens of prostatic adenocarcinoma. BJU Int 1999;84:851-3.
5. Karja V, Aaltomaa S, Lipponen P, Isotalo T, Talja M, Mokka R. Tumour-infiltrating lymphocytes: A prognostic factor of PSA-free survival in patients with local prostate carcinoma treated by radical prostatectomy. Anticancer Res 2005;25:4435-8.
6. Vesalainen S, Lipponen P, Talja M, Syrjanen K. Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur J Cancer 1994;30A:1797-803.
7. Shimura S, Yang G, Ebara S, Wheeler TM, Frolov A, Thompson TC. Reduced infiltration of tumor-associated macrophages in human prostate cancer: association with cancer progression. Cancer Res 2000;60:5857-61.

Written by Fred Saad, MD, FRCS as part of Beyond the Abstract on UroToday.com

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