Lung cancer's molecular features shed light on immunotherapy response (Simple-to-find characteristics point to therapy success)

Medical Xpress / Broad Institute of MIT and Harvard / Nature Genetics ^ | April 19, 2023 | Karen Zusi-Tran / Arvind Ravi et al

[ConservativeMind]

One of the newest types of cancer drugs, immunotherapies called immune checkpoint inhibitors, has transformed the treatment of lung cancer over the last decade—dramatically improving the survival of some patients with the most common form of this disease, non-small cell lung cancer (NSCLC). However, only about 20% of patients experience a benefit.

A new study reveals key molecular features of lung tumors that could explain why some patients respond to these treatments while others do not. The team has pinpointed factors that may influence the response of NSCLC patients to immunotherapies that inhibit the PD-1 or PD-L1 proteins.

The PD-1/PD-L1 immune checkpoint is a protein interaction that normally suppresses the immune system. Cancer cells use this mechanism to evade the body's defenses. Anti-PD-(L)1 agents work by blocking this interaction, stimulating the immune system to attack cancer cells.

By integrating the clinical, genomic, and transcriptomic data, the researchers uncovered two overall collections of features that correlated with a favorable treatment response: an "immune activated/exhausted" environment, in which the immune cells displayed signatures of previously high activity that had waned; and a signature defined by high levels of neoantigens, or foreign proteins displayed on the surface of the tumor cells.

A third category—a "wound healing" microenvironment, in which the immune system appeared dampened, similar to how it would behave in the early stages of healing a physical injury—was associated with an unfavorable response to treatment.

"These features could provide the ability to stratify patients," explains Ravi. "We found patients whom you would expect to respond well to therapy based on traditional predictors may actually respond poorly, due to the presence of additional unfavorable factors that are not usually assessed in routine clinical care. Understanding this complex architecture will continue to be critical as we investigate how to improve outcomes in all patients."

[ConservativeMind]

The key quote:

“…the researchers uncovered two overall collections of features that correlated with a favorable treatment response: an "immune activated/exhausted" environment, in which the immune cells displayed signatures of previously high activity that had waned; and a signature defined by high levels of neoantigens, or foreign proteins displayed on the surface of the tumor cells.”

Your doctor or oncologist can easily identify these characteristics to determine if immune checkpoint inhibitors will work for you, or if a different approach is then needed.

[ConservativeMind]

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[ComputerGuy]

I start chemo and radiation next Monday. I’ll point this out to my oncologist. He’s kept me alive for the last 9.5 years with some novel treatments.

[irishjuggler]

Good luck. And prayers for you.

[ComputerGuy]

Thank you.

[Falconspeed]

“immunotherapies that inhibit the PD-1 or PD-L1 proteins.” Very interesting. Worth a try. There’s always hope. The scholars at MIT are brilliant focusing on PD1 and PDL1 proteins are hopeful.

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[BBB333]

Best of luck to you.

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