Nathan Pennell: Incredible effort from investigators all over the world on this paper

A recent paper by Ferdinandos Skoulidis et al. was published in Nature Journal.

“CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors.”

Authors: Ferdinandos Skoulidis, Haniel Araujo, Minh Truong Do, Philip Jewsbury, John Heymach et al.

In advanced NSCLC, patients with mutations in the STK11 and/or KEAP1 genes respond better to dual immune checkpoint blockade (ICB) using a combination of a PD-L1 inhibitor (durvalumab) and a CTLA4 inhibitor (tremelimumab), along with chemotherapy, compared to using a PD-L1 inhibitor alone.

The phase III POSEIDON trial demonstrated that these genetic alterations are linked to resistance against PD-(L)1 inhibitors, but dual ICB can overcome this resistance.

This combination therapy reprograms the tumor microenvironment, shifting immune cells towards more effective anti-tumor responses, particularly involving CD4+ effector cells and tumoricidal myeloid cells, leading to improved clinical outcomes.

Nathan Pennell, Professor and Thoracic Medical Oncologist at Cleveland Clinic, shared a post on LinkedIn about the paper:

“Incredible effort from investigators all over the world on this paper!”

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