Combination of Cells Improves Immunotherapy

Aug 27, 2018 10:11:00 AM by Stacy Matthews Branch, DVM, PhD

Stem cell research for the treatment of cancer_AdobeStock_190278636-971852-editedA recent study looked at how checkpoint inhibitors may impact the success of immunotherapy for cancer treatment.

Immune homeostasis is crucial for human and animal survival. The immune system is equipped with cells and factors that maintain a critical balance of signals that prevent immune dysfunction. Pathways that ensure this balance are immune checkpoints, and these are essential for the self-tolerance that prevents autoimmunity. Immune checkpoint proteins modulate T-cell responses to self-proteins and antigens, including tumor antigens. The proteins are expressed on the surface of cancer and cytotoxic T cells, and cancer cells use these to evade attack by T cells.

Checkpoint inhibitors have been developed that block checkpoint proteins such as programmed cell death protein 1 (PD-1) found on T cells. Between 20 and 40% of patients treated with checkpoint inhibitors respond favorably. That means that a large percentage of patients do not respond well to treatment with checkpoint inhibitors. Results of a recent study suggest that favorable responses to checkpoint-inhibitor cancer therapy is more likely in patients with a combination of specific immune cell types in their tumors.

In the study, researchers analyzed tumor biopsies from patients with metastatic melanoma and who were treated with PD-1 immunotherapy. Clinical outcome and patient responsiveness to anti-PD-1 therapy was tracked. Biopsy analysis of SDC abundance was analyzed and correlated to patient outcome. They found that SDC levels were positively associated with favorable patient response to therapy.

Yet another cell type was found to be important in the responsiveness to checkpoint-inhibitor therapy. This was discovered when the researchers studied a melanoma mouse model depleted with T cells or natural killer (NK) cells. No change in the level or cellularity of SDCs were detected in mice lacking T cells. On the other hand, reduced frequencies of SDCs were observed in the tumors of mice depleted of NK cells. This shows that NK cells control SDC levels, and SDC levels subsequently correlate with patients’ response to anti-PD-1 immunotherapy. These results are promising and can lead to the development of approaches to activate tumor NK cells to enhance checkpoint-inhibitor therapy and to identify biomarkers prognostic of checkpoint-inhibitor treatment response.

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Combination of Immune Cells Improves Immunotherapy Success — Study. (2018). Immuno-Oncology News. Retrieved 16 July 2018, from