Inflammation is known to be a significant player in cancer progression. This study pinpointed that a high neutrophil-to-lymphocyte ratio (NLR) in the blood, which indicates peripheral blood myeloid expansion, is linked to shorter survival rates and treatment resistance across a variety of cancers and therapeutic approaches. However, the role of myeloid inflammation in prostate cancer progression has remained a grey area until this investigation.
The team discovered that a higher blood NLR mirrors an increase in tumour myeloid infiltration and tumour expression of certain molecules associated with myeloid chemoattracting. In a bid to ascertain whether myeloid cells contribute to resistance against androgen receptor signalling inhibitor (ARSI), and if blocking myeloid chemotaxis could reverse this, they carried out a clinical trial. They tested a combination of a CXCR2 inhibitor (AZD5069) and enzalutamide in patients with ARSI-resistant mCRPC.
The combination was well tolerated by the patients, without any dose-limiting toxicity. It led to a decrease in circulating neutrophils, reduced intratumour myeloid cell infiltration, and imparted durable clinical benefits with biochemical and radiological responses in a subset of mCRPC patients. This pioneering study provides the first clinical evidence that senescence-associated myeloid inflammation can fuel mCRPC progression and resistance to AR blockade. The findings suggest that targeting myeloid chemotaxis could be a viable strategy, meriting broader evaluation in other types of cancer as well.
This study brings a fresh perspective to the table, opening up avenues for further research in not only prostate cancer but potentially other cancers too, making strides towards a more optimistic future in cancer treatment advancements.
Nature. 2023 Oct 16.
Christina Guo, Adam Sharp, Bora Gurel, Mateus Crespo, Ines Figueiredo, Suneil Jain, Ursula Vogl, Jan Rekowski, Mahtab Rouhifard, Lewis Gallagher, Wei Yuan, Suzanne Carreira, Khobe Chandran, Alec Paschalis, Ilaria Colombo, Anastasios Stathis, Claudia Bertan, George Seed, Jane Goodall, Florence Raynaud, Ruth Ruddle, Karen E. Swales, Jason Malia, Denisa Bogdan, Crescens Tiu, Reece Caldwell, Caterina Aversa, Ana Ferreira, Antje Neeb, Nina Tunariu, Daniel Westaby, Juliet Carmichael, Maria de los Dolores Fenor de la Maza, Christina Yap, Ruth Matthews, Hannah Badham, Toby Prout, Alison Turner, Mona Parmar, Holly Tovey, Ruth Riisnaes, Penny Flohr, Jesus Gil, David Waugh, Shaun Decordova, Anna Schlag, Bianca Calì, Andrea Alimonti & Johann S. de Bono