Whole Body Scans May Help Reveal Which Patients Will Respond to Immune Checkpoint Inhibitors

A new study may help to reveal which patients with cancer will respond to treatment with immune checkpoint inhibitors (ICIs). Despite the remarkable success of ICIs in harnessing the immune system to fight tumors, patient response to these therapies is unpredictable, according to the study, published in Nature Medicine.

“Immune checkpoint inhibitors release the full power of T-cells on tumors,” Liesbeth de Vries, professor of Medical Oncology at the University Medical Centre Groningen, said in a press release. “We would like to know early on which patients do not respond and maybe need some additional activation of their immune system.”

For the study, investigators performed whole-body PET scans with a radioactively labeled antibody tracer, primarily against CD8+ T-cells, prior to and 30 days following the start of ICI treatment. After showing that the tracer binds to CD8+ T cells, the researchers found that CD8+ T cell presence is both heterogeneous and dynamic, which may help to guide future treatment decisions.

The immune system eliminates intruders, such as micro-organisms, as well as cells that have changed to become unrecognizable. The immune system can also attack tumor cells, which is a challenge because tumors are able to silence T-cells to prevent tumor infiltration, the authors wrote. They noted that the discovery of pathways to eliminate this immune suppression is a significant breakthrough in cancer therapy.

The study authors used whole body PET scans with half of an antibody structure targeted against CD8+ and labeled with zirconium-89.

“Activated T-cells are everywhere in the entire body, but so far, our knowledge about their distribution was largely based on biopsies,” de Vries said. “We wanted to study the full picture.”

Tumor biopsies from patients confirmed the accuracy of the PET scan results, indicating that tracer uptake is a good measure of immune activation, according to the study authors.

“We compared the amount of radioactivity in the biopsies measured by autoradiography with staining for CD8+ cells,” de Vries said. “And we found higher tracer uptake in lesions with high CD8+ infiltration.”

These findings prompted the researchers to evaluate whole body scans, which indicated that the upfront presence of CD8+ cells predict the outcome for the patient.

“We were stunned by the heterogeneity in response we saw, both within individual patients and between patients,” De Vries said.

This study is the first to analyze the whole-body response in patients administered ICIS; however, the findings are complicated, according to the authors.

“It was generally assumed that around 30 days of treatment there would be a clear-cut difference between responders and non-responders in CD8+ T-cell presence, but that was not the case,” De Vries said. “The response is much more dynamic, with a large spatial and temporal variation in the presence in tumor lesions of activated T cells.”

As ICIs are increasingly showing efficacy across a broad range of cancer types, determining which patients will respond to treatment is vital.

“The field is rather overwhelming. These drugs are now being used not just as a last resort, but also evaluated to prevent metastasis or to reduce tumor size before an operation,” De Vries concluded.

Reference

Kist de Ruijter, L., van de Donk, P.P., Hooiveld-Noeken, J.S. et al. Whole-body CD8+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial. Nat Med (2022). https://doi.org/10.1038/s41591-022-02084-8