Piotr Wysocki recently shared on LinkedIn:

“Mariniello A. et al. published results of an important preclinical study in Clinical Cancer Research. The authors used a mouse model of T-cell exhaustion to assess the effect of chemotherapy (cisplatin+pemetrexed) on T-cell response to PD-1 blockade.

Concomitant use of chemotherapy and PD-1 blockade resulted in:

• Impaired differentiation of antigen-specific CD8 T cells from stem-like to transitory effector cells
• Reduction of CD8 T cell expansion and IFNγ production
• Impaired CD8 T cell effector function (viral control)

Sequential use of chemotherapy followed by PD-1 blockade resulted in:

• Reserved proliferative responses of exhausted CD8 T cells to PD-1 blockade
• Quiescent (PD-1-mediated) state of CD8 T cells protecting them from chemotherapy-induced functional impairment

The study by Mariniello A. et al. provides a strong translational proof-of-concept to consider optimizing the timing of chemo-immunotherapy strategies for improved CD8 T-cell functions by postponing the use of immunotherapy after completion of chemotherapy. An excellent example of this sequential strategy is the history of immunotherapy in urothelial cancer, where many trials on concomitant chemoimmunotherapy failed to improve patients’ survival.

However, immunotherapy used as maintenance after chemotherapy (avelumab in JAVELIN Bladder 100) or in a second-line setting (pembrolizumab in KEYNOTE-045) significantly improved long-term outcomes.”

Platinum-Based Chemotherapy Attenuates the Effector Response of CD8 T Cells to Concomitant PD-1 Blockade

Authors: Annapaola Mariniello, Tahseen H. Nasti, Daniel Y. Chang, Masao Hashimoto, Sakshi Malik, Daniel T. McManus, Judong Lee, Donald J. McGuire, Maria A. Cardenas, Pablo Umana, Valeria Nicolini, Rustom Antia, Ananya Saha, Zachary Buchwald, Hayden Kissick, Ehsan Ghorani, Silvia Novello, Dario Sangiolo, Giorgio V. Scagliotti, Suresh S. Ramalingam, Rafi Ahmed

Source: Piotr Wysocki/LinkedIn

Piotr Wysocki leads the Clinical Oncology Department at University Hospital and the Faculty of Oncology at Jagiellonian University-Medical College in Krakow, Poland. As an advisor to the Polish Ministry of Health, he shapes the national cancer strategy.

His clinical expertise spans the systemic treatment of breast, gynecologic, and genitourinary cancers, with a focus on developing innovative metronomic chemotherapy-based therapies for advanced cancer patients who have undergone prior treatment.

Read other posts by Piotr Wysocki published on OncoDaily.