Tumor-dwelling immune cells thwart cancer immunotherapy

May 10, 2017

Researchers have caught tumor-associated immune cells called macrophages in the act of stealing checkpoint inhibitor antibodies away from their intended T cell targets, and blocking this thievery led to improved therapeutic responses in tumor-bearing mice. Immune checkpoint blockade therapies have been shown to be tremendously helpful in treating multiple malignancies including non-small cell lung, bladder, and skin cancers, but not all patients respond to these treatments. Here, Sean Arlauckas and colleagues discovered one potential reason why checkpoint blockade antibodies sometimes fail to prevent T cell exhaustion, and as a result cannot unleash the immune system against cancer. The researchers used intravital imaging to peer inside tumors in living mice, where they observed macrophages that removed checkpoint blockade antibodies from T cells. Similar antibody-stealing occurred in a culture system composed of human cells together with the currently approved cancer immunotherapy, nivolumab. Interestingly, macrophages typically gobble up invading pathogens and debris, though the researchers determined that the cells were capturing checkpoint blockade antibodies through a separate process involving a surface receptor called FcγR. Blocking FcγR allowed checkpoint inhibitor antibodies to interact with T cells in both rodents and human cells growing in culture. What's more, co-treatment with checkpoint inhibitors and FcγR blocking antibodies led to a 100% response rate in a mouse model of cancer that typically displays substantial animal-to-animal variability in therapeutic outcomes. The authors say therapeutic regimens designed to target tumor macrophages may enhance the activity of immunotherapies, providing additional benefit by increasing immune checkpoint blockade drug delivery.
-end-


American Association for the Advancement of Science

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.