Date of Award


Degree Type


Degree Name

Doctor of Philosophy


73 samples of H&NSCCa were processed for these studies. An enzymatic disaggregation protocol for the flow cytometric analysis of DNA content of tumour whole cell preparations was developed. Analysis of the tumour cell component without the need for incorporation of reference controls provided a more accurate assessment of DNA content of tumour cell populations. Six lines of H&NSCCa were established in vitro from fresh tumour samples. Tumour cell effects on PHA- or IL-2 stimulated proliferation of PBMNCs ranged from 61% and 45% suppression to 4% and 121% enhancement of the proliferative responses respectively. Flow cytometric analysis revealed a down regulation of expression of the IL-2 receptors in PHA-stimulated PBMNCs exposed to tumour cells. The prostaglandin inhibitor, indomethacin, was found to reverse the suppression of PHA- and IL-2-stimulated proliferation. TILs were expanded in vitro using IL-2 and used as effector cells. A {dollar}\sp{lcub}14{rcub}{dollar}C adenine radioactive tracer release assay for adherent cell lines was adapted for anti-tumour cytotoxicity experiments. Although tumours were insensitive to natural killer (NK) cell killing, a broad spectrum of sensitivity to killing by IL-2 stimulated cells was noted. When compared to patient or volunteer LAK cells, expanded TILs were consistently poorer effectors of tumour lysis. Clones of TILs which were capable of killing autologous tumour cells were isolated for three of the six tumour lines. This killing was of the same magnitude as that of control allogeneic LAK cells and was unrestricted to the autologous tumour. Cytotoxic clones were consistently CD3+, NKH-1+ and CD4+ or CD8+. Cytocidal ability of the clones remained very stable in comparison to unselected LAK populations which lost cytotoxic capability over time (6 weeks). Immunotherapeutic regimens must take into account the wide heterogeneity of tumour-immune interactions demonstrated in this system. While the suppressive capability of these tumours and their variable sensitivity to killing by effector cells is daunting, the demonstration of effective generation of anti-tumour clones suggest in situ anti-tumour responses which can be potentially exploited for immunotherapy.



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