This year, the International Union of Immunological Societies has partnered with Immunopaedia and Frontiers in Immunology to host a series of webinars on different topics in the field of Immunology (Webinar series sponsored by Thermo Fisher Scientific). The first webinar of the year featured a talk by Pamela Ohashi on “Immunoregulation and the tumour microenvironment”. The full webinar is available below.
By loading the video, you agree to YouTube's privacy policy.
Learn more
Prof. Ohashi presentation focused on PD-1 blockade, specifically why PD-1 based immunotherapies work for some cancers but not others. She began with an overview of PD-1 and how its interaction with PD-L1 (on antigen presenting cells) can affect T cell function. Although PD-1 blockade has transformed cancer treatment, some cancers such as head and Neck; non-small cell lung, kidney and ovarian cancers, among others, do not respond to PD-1 blockade immunotherapy. Improving PD-1 based cancer immunotherapy requires a deeper understanding of the role of PD-1 in different tumour microenvironments.* Prof Ohashi presented data that compared responses between ovarian and melanoma cancers, cancers that respond poorly and favourable to PD-1 blockade, respectively. This comparison aimed to identify factors/mechanisms that explain why some tumours don’t respond well to PD-1 blockade.
Studies have shown that poor tumour infiltration of T cells is associated with poor prognosis epithelial ovarian cancer (Zhang et al., 2003 NEJM). Thus suggesting that improving T cell infiltration could improve cancer prognosis. Interestingly, they observed T-regs found in ovarian cancer expressed higher levels of PD-1 and FoxP3 and superior anti-inflammatory activity than T-regs in melanoma cancer and peripheral blood (see image). She next presented data that investigated expression patterns of PD-L1, B7-H3 and B7-H4 on biopsies from ovarian cancer. She showed data that demonstrated high expression of B7-H3 on stromal cells compared with tumour cells, while expression of B7-H4 was higher in tumour compared to stromal cells. Interestingly, PD-L1 was not expressed on tumour cells but was expressed on stromal cells. Thus, potentially suggesting why PD-L1 blockade does not work as well for ovarian cancer therapy, further, it highlights potential implication for combination therapies.
Lastly, she described a population of innate lymphoid cells that have regulator capacity (inhibited CD4 and CD8 T cells via NKp46), express high levels of CD56+ and produced IL-22 and IL-9, which she termed ILC-regs. These cells also expressed high levels of CD7, 2B4 and TIM-3, phenotypes associated with limiting tumour infiltrating lymphocytes (TIL) expansion and slow-growing breast cancer cultures in vitro. She further highlighted that tumours associated with different cancers have different micro-environment, such as higher proportions of CD4+ T cells but lower levels of CD3+ T cells in fast-growing breast cancer cultures.
She ended her talk suggesting that the potential barrier to PD-1 blockade mono-therapy in ovarian cancer could be due to higher proportions of activated T-regs and ILCregs that may interfere with tumour immunity during PD-1 blockade.