A35
CD8+ T cell function in cancer patients receiving chemotherapy
Richard Lake, Mel McCoy, Anna Nowak
School of Medicine & Pharmacology, UWA; National Centre for Asbestos Related Research, Nedlands, Australia
Background
Chemotherapy and immunotherapy have usually been considered antagonistic treatment options because of the variable lymphopaenia experienced as a side effect of many cytotoxic drugs. Recently however, research using animal models has demonstrated that some chemotherapy drugs, despite causing decreases in lymphocyte numbers, can actually enhance the anti-cancer immune response, possibly via the induction of immunogenic tumour cell death. The generation of an immune response to a tumour critically depends upon the appropriate presentation of tumour antigens to CD8+ effector T cells, which can then kill tumour cells directly.
Method
We wanted to determine the effect of different chemotherapy regimes on the anti-tumour immune response in patients with malignant mesothelioma or non-small cell lung cancer so that we could optimize an adjunct immunotherapeutic approach. We therefore measured the number and functional status of peripheral blood CD8+ T cells during the course of treatment with cisplatinum and pemetrexed. We monitored changes in the proportion of T cell subsets and assessed activation and proliferation status using 8 parameter flow cytometry.
Results
36 patients have been recruited and peripheral blood samples from the first 22 patients have been analysed. Following an initial decrease 1 week into treatment, the proportion of proliferating CD8+ T cells, increased in most (19/22) patients after completion of one 3-week cycle of chemotherapy (median increase 38% of baseline value IQR 9,100). A further increase was observed after 3 cycles (median increase 58% of baseline value IQR 18,139). In some patients, a population of activated CD8+ effector T cells that were not present before treatment could be identified following treatment.
Conclusion
These data support the notion that chemotherapy can augment anti-tumour immunity and suggest that neoadjuvant immunotherapy could be combined with standard chemotherapy to improve responses.
