How Proteasomes are Changing the Face of Cancer Immunotherapy

Cancer immunotherapy is revolutionizing treatment by harnessing the power of the body’s own immune system to recognize, target, and eliminate cancer cells. While it has transformed treatment for many cancer types, it is not a one-size-fits-all solution. Each cancer is unique, and each patient’s response to immunotherapy varies. This differentiation hinges on factors like cancer type, genetic makeup, and surprisingly, how cancer cells handle protein waste.

Proteins are the vital building blocks of all cells, including cancerous ones, driving countless cellular processes. Cancer cells hijack protein metabolism to fuel their relentless growth and multiplication. They also collect abnormal amounts of proteins and their waste. In healthy cells, these protein wastes are degraded in specialized protein destruction centers called proteasomes. With cancer, these proteasomes often malfunction, leading to unchecked protein buildup.

Proteasomes play a critical role in tumor immune response by regulating inflammatory signals, activating immune cells, and processing and presenting antigens. Understanding how proteasome changes impact immunotherapy response is a flourishing research area.

Recent research indicates that higher levels of specialized proteasomes, called immunoproteasomes, are linked to better immunotherapy outcomes in melanoma patients. Scientists believe that advancing proteasome-targeting strategies could lead to more potent and effective immunotherapies.

CRI Lloyd J. Old STAR Yifat Merbl, PhD, from the Weizmann Institute of Science, is at the forefront of studying proteasomes and their influence on immunotherapy. Dr. Merbl explores how proteasome-driven protein degradation shapes cancer and its response to immunotherapy. She has identified various regulatory subunit caps that control proteasome function in cancer cells.

Using mass spectrometry to analyze proteasome-cleaved peptides, Dr. Merbl is mapping the proteasome composition and protein degradation landscape of tumors by isolating the actively degrading peptides within cellular proteasomes.

Speaking recently to CRI, Dr. Merbl declared, “Our efforts will uncover regulatory mechanisms underlying the potential for modulating tumor degradation as a novel intervention in cancer immunotherapy.” By employing cutting-edge research techniques and a bold, innovative approach, Dr. Merbl and other CRI-funded scientists are trailblazing the path to novel precision oncology interventions. “Ultimately, CRI’s funding will help us translate our scientific findings into innovative treatments, potentially offering new hope to cancer patients,” Dr. Merbl added.

By delving into proteasomes and protein degradation across different cancers, scientists like Dr. Merbl can uncover the cellular and molecular programs affected by various proteasome complexes and degradation processes. This groundbreaking knowledge can be harnessed to develop superior immunotherapies and ultimately, a world immune to cancer.