New Insights into Why Some Cancer Patients Do Not Respond to Personalized Immunotherapy and a Promising Vaccine Development

A recent groundbreaking study has shed light on the mechanisms behind the resistance to immune-checkpoint therapy (ICT) observed in some cancer patients. While ICT, which revitalizes the patient’s own immune system to target cancer cells, has significantly advanced the field of oncology over the past twenty years, a considerable number of patients do not experience benefits, often due to tumors that evade immune detection, termed "cold" tumors.

The research, led by Dr. Scott Lippman from the University of California San Diego, emphasizes the critical importance of identifying non-responders and unraveling the genetic and molecular underpinnings of such resistance. In particular, the study highlights the role of loss of genetic material on chromosome arm 9p, which contributes to immune-evasion by reducing key signaling molecules like CXCL9 and CXCL10—chemokines essential for attracting immune cells to the tumor microenvironment.

Building upon previous work that linked 9p loss to resistance in head and neck cancers, the new study extends these findings to other cancers including lung, melanoma, mesothelioma, and bladder cancer. Loss of 9p not only impairs immune cell infiltration but also correlates with specific deficiencies in type-I interferon genes, especially IFNε, which are located on chromosome 9p. This deficiency hampers the tumor's ability to produce signals necessary for attracting immune cells.

Moreover, the study reveals that tumors tend to undergo homozygous deletion of 9p more frequently than other chromosomal regions, suggesting a selective pressure for removing interferon genes to escape immune detection. This genomic alteration, therefore, acts as an evolutionary adaptation that challenges current immunotherapies.

Encouragingly, these insights have sparked the development of novel cancer vaccines aimed at overcoming immune suppression. One promising approach involves using engineered dendritic cells to bypass the depletion of critical chemokines and re-activate immune responses in 9p-loss tumors. Recognified in preclinical models, this strategy holds potential for future clinical applications.

Overall, this research by Lippman's team not only deepens understanding of immune-evasion mechanisms but also opens new avenues for personalized treatments. Targeting the specific genetic and molecular features responsible for resistance could enhance the effectiveness of immunotherapy, ultimately leading to better outcomes for cancer patients.

Source: https://medicalxpress.com/news/2025-09-cancer-patients-personalized-immune-therapy.html