Exploring the Benefits of Immunotherapy for Cancer Patients

The study offers fresh insights into the mechanism by which PD-1 blocking agents functions to maintain healthy tissues ().

The key finding could help researchers predict, treat, or even prevent the side effects of PD-1 blocking immunotherapies.

Cancer Immunotherapy
Cancer immunotherapy is a new advancement in cancer treatment that uses certain components of a person's immune system to fight against cancer cells.

‘PD-1 has a significant role in blocking T cells from attacking normal tissues in healthy people and may help prevent the side effects of immunotherapy. #cancer’

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Role of PD-1 Receptors in Cancer

Cancer immunotherapy has revolutionized treatment of many forms of cancer by unleashing the immune system response against tumors. Immunotherapies that block checkpoint receptors like PD-1, proteins that limit the capacity of T cells to attack tumors, have become the choice for the treatment of numerous types of solid cancer. However, the introduction of PD-1-blocking agents can often result in T cells attacking healthy tissues in addition to cancer cells, causing severe, sometimes life-threatening, side effects that can blunt the benefits of immunotherapy.

The study was published in the journal Nature.

“While we know why blocking checkpoint receptors boosts anti-cancer immune responses, we don’t understand why these immunotherapies also cause adverse events in normal organs,” the authors write.

CAR T-Cell Therapy - Novel Form of Immunotherapy
CAR T-cell therapy is a type of gene therapy where the patient’s T-lymphocytes are genetically altered to target cancer cells within the patient’s body.

Currently doctors are not able to predict which individuals are likely to develop such side effects and which healthy organs will be attacked as a consequence of immunotherapy. Side effects may prompt doctors to either suspend immunotherapy or prescribe immunosuppressants, with negative consequences on the anti-cancer effects of immunotherapy.

For the study, a team led by Martina Damo, an associate research scientist in the Joshi lab, developed new generation mouse models to address the role of PD-1 in preventing T cells from attacking healthy skin. They mimicked immunotherapy by blocking PD-1 and found mice developed some of the same skin disorders observed in cancer patients treated with PD-1 blockers.

Test Your Knowledge on Immunotherapy Drugs
Immunotherapy is a type of treatment method that works by using certain components of a person's immune system to treat the disease.

There are two ways by which these therapies work:

Activation immunotherapies work by enhancing or stimulating the immune system. Examples in this category work to destroy cancer cells.
Suppression immunotherapies work by inhibiting or suppressing the immune system. Examples in this category are used to treat allergies and autoimmune diseases.

Test your knowledge and know more about immunotherapy drugs by taking this quiz.

The data in mice were corroborated by analysis of skin biopsies obtained from cancer patients under treatment at the Yale Onco-Dermatology Program at Smilow Cancer Hospital at Yale New Haven, which is directed by Dr. Jonathan Leventhal.

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“Our data in mice and humans support the hypothesis that checkpoint receptors like PD-1 function as gatekeepers of tissue homeostasis by allowing the presence of functional T cells in peripheral tissues without immunopathology,” Damo said. “We propose that PD-1-blocking immunotherapies interfere with these physiological regulatory functions, thus resulting in adverse events. This study lays the ground for the future development of improved immunotherapies that avoid adverse events.”

Reference:

PD-1 maintains CD8 T cell tolerance towards cutaneous neoantigens - (https://www.nature.com/articles/s41586-023-06217-y)

Source-Eurekalert