Neoadjuvant Chemotherapy and the Immune Landscape in Early-Stage Breast Cancer

By: Jenna Carter, PhD
Posted: Tuesday, January 17, 2023

A recent study, which was presented at the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 97) and published in the Journal for ImmunoTherapy of Cancer, highlighted the impact of neoadjuvant chemotherapy on the immune landscape of patients with newly diagnosed early breast cancer. Bernardo Rapoport, MD, of the University of Pretoria, South Africa, and colleagues examined alterations in plasma concentrations of 16 soluble co-stimulatory and co-inhibitory immune checkpoints. Findings revealed that levels of five co-stimulatory and three co-inhibitory soluble checkpoints were significantly lower in patients with breast cancer compared with healthy controls.

“Neoadjuvant chemotherapy…may alter the immune landscape of patients with early breast cancer… potentially setting the scene for more effective implementation of checkpoint-targeted immunotherapy, albeit by largely unexplored mechanisms,” stated Dr. Rapoport and colleagues.

A total of 72 patients with newly diagnosed breast cancer were enrolled in this study. Plasma samples were collected before treatment, after neoadjuvant chemotherapy, and after surgery. Samples were then characterized using a multiplex bead array platform. A total of 16 soluble co-stimulatory and co-inhibitory immune checkpoints were measured and compared with a group of healthy controls (n = 45).

Overall findings revealed that the median pretreatment levels of five co-stimulatory (CD27, CD40, GITRL, ICOS, GITR) and three co-inhibitory (TIM-3, CTLA-4, PD-L1) soluble checkpoints were significantly lower in patients with breast cancer compared with controls (P < .021 to < .0001 and P < .008 to < .00001), respectively. Following neoadjuvant treatment, the plasma levels of six soluble co-stimulatory checkpoints involved in activation of CD8-positive cytotoxic T cells were significantly increased relative to pretreatment levels (P < .04 to < .00001). Three soluble co-inhibitory checkpoints (LAG-3, PD-L1, TIM3) increased significantly after neoadjuvant chemotherapy; however, PD-1 was unchanged, and BTLA and CTLA-4 were significantly decreased (P < .03 and P < .00001). These findings suggest compensatory changes in the co-stimulatory and co-inhibitory immune systems as they seek to restore balance after neoadjuvant chemotherapy.

Disclosure: No disclosure information was provided.

Journal for ImmunoTherapy of Cancer

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