Myeloid cell networks govern re-establishment of original immune landscapes in recurrent ovarian cancer
Women unfortunate enough to develop a recurrence of ovarian cancer show a range of responses to repeat chemo. This study looks at the immune response to the cancer and the survival outcomes.
About half of these women show the presence of tumour infiltrating lymphocytes, (TIL), suggesting an active cell-mediated immune response. This is associated with better survival. Most of those women also display defective DNA repair with Homologous Recombination Deficiency (HRD). The immune response is stimulated by increased antigens such as PD-1, which suggest that immunotherapy with immune checkpoint inhibitors could be of benefit. However, in practice this has not seen to be true.
To understand why this is the case the authors reviewed the immune status of abut 600 patients with ovarian cancer using digital pathology. They subdivided the immune response into 4 groups from high to low.
In the presence of HRD, cell-mediated immunity is increased with inflammation. When treated with chemo and PARP inhibitors, prostaglandin E prevents TIL activity by cell death called ferroptosis. Using a mouse model the researchers were able to prevent this using ant-inflammatories and restore the immune response.
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