Researchers have suggested a way of reducing the risk of infection faced by cancer patients receiving immune checkpoint inhibitor treatment.
The research, published in the journal Immunity, points to B cells being affected by the treatment, meaning that immunity developed during previous infections is lost.
The study has been undertaken at the Garvan Institute of Medical Research in New South Wales, Australia, by a team working with researchers at Kyoto University, Japan, and Rockefeller University, New York, USA.
The researchers suggest that doctors treating patients with the drugs need to monitor B cell function. Immunoglobin replacement therapy might help to replenish antibody levels, they suggest.
The findings come from a study of the PD-1 molecule, which is blocked by checkpoint inhibitors to activate T cells against cancer cells. The researchers studied patients with a genetic deficiency of PD-1 and also undertook laboratory studies. They found that impaired PD-1 activity reduced the diversity and quality of antibodies produced by memory B cells.
Researcher Dr Masato Ogishi, from Rockefeller University, said: “We found that people born with a deficiency in PD-1 or PD-L1 have reduced diversity in their antibodies and fewer memory B cells, which made it harder to generate high-quality antibodies against common pathogens such as viruses and bacteria.”
Fellow researcher Professor Stuart Tangye, from Garvan, said: “Immune checkpoint inhibitor therapies have revolutionised cancer treatment by allowing T cells to attack tumours and cancer cells more effectively. But this hasn’t been without side effects – one of which is that approximately 20% of cancer patients undergoing checkpoint inhibitor treatment experience an increased incidence of infections, a phenomenon that was previously poorly understood.
“Our findings indicate that while checkpoint inhibitors boost anti-cancer immunity, they can also handicap B cells. This understanding is a critical first step in understanding and reducing the side effects of this cancer treatment on immunity.”
Professor Tangye added: “This dampening of the generation and quality of memory B cells could explain the increased rates of infection reported in patients with cancer receiving checkpoint inhibitor therapy.”
Source:
Ogishi M, Kitaoka K, Good-Jacobson KL, Rinchai D, Zhang B, Wang J, Gies V, Rao G, Nguyen T, Avery DT, Khan T, Smithmyer ME, Mackie J, Yang R, Arias AA, Asano T, Ponsin K, Chaldebas M, Zhang P, Peel JN, Bohlen J, Lévy R, Pelham SJ, Lei WT, Han JE, Fagniez I, Chrabieh M, Laine C, Langlais D, Gruber C, Al Ali F, Rahman M, Aytekin C, Benson B, Dufort MJ, Domingo-Vila C, Moriya K, Shlomchik M, Uzel G, Gray PE, Suan D, Preece K, Chua I, Okada S, Chikuma S, Kiyonari H, Tree TI, Bogunovic D, Gros P, Marr N, Speake C, Oram RA, Béziat V, Bustamante J, Abel L, Boisson B, Korganow AS, Ma CS, Johnson MB, Chamoto K, Boisson-Dupuis S, Honjo T, Casanova JL, Tangye SG. (2024) “Impaired development of memory B cells and antibody responses in humans and mice deficient in PD-1 signalling.” Immunity, 26 November 2024, doi: 10.1016/j.immuni.2024.10.014.
Link: https://www.cell.com/immunity/abstract/S1074-7613(24)00495-3
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