Lymphoid cell infiltration during breast cancer growth: A syngeneic rat model

The systematic study of potential alterations in lymphoid infiltrates durin g tumour growth is extremely limited in humans. Therefore, development of a model utilizing a spontaneously arising mammary adenocarcinoma in Dark Ago uti rats was adopted for the study of the dynamics of lymphoid cell infiltr ation during tumour development. Syngeneic rats were inoculated with tumour cell suspensions and the tumours were resected from 5 to 15 days. Serial s ections were immunohistochemically stained using a panel of monoclonal anti bodies. Irrespective of tumour age, ED2 (macrophages) and W3/25 (CD4)-posit ive cells were the most prominent cell infiltrates in tumours. There were n o significant differences in cell counts for any marker between 8-day and 1 5-day tumours. However, in 5-day tumours there were significantly fewer mac rophages, OX19(+) T cells, W3/25(+) cells, OX8(+) (CDS) cells and OX62(+) d endritic cells. Interleukin-2 receptor alpha chain expression was low at al l examined stages of tumour growth, indicating a lack of tumour infiltratin g lymphocyte (TIL) activation and/or possible TIL anergy. B cell staining w as absent in all tumours, negating the possibility of these cells mediating coregulatory signals for TIL activation in the micro-environment of establ ished tumours. The results parallel previous immunohistochemical findings i n humans, suggesting that a dysfunctional local immune response in breast c ancer may be determined very early during tumour development.