Neutrophils Found to Protect Lung Cancer Cells

Targeting the microenvironment of lung cancer tumors with immunotherapies show promise.

Findings from a new study published by Nature Communications suggest that the microenvironment in tumors may be crucial for the survival of cancer, not just the cancer cells themselves.

Cancer cells are able to recruit healthy cells to build a wall around tumors, while others can create new blood vessels. The tumor microenvironment—noncancerous cells that are critical for cancer survival—may play a role in how well therapies work, especially immunotherapy, according to the authors.

“Tumor microenvironment issues come hand-in-hand with working on solid tumors,” said researcher Kristin Anderson, PhD.

Immunotherapies such as pembrolizumab (Keytruda) work by bringing new life to T cells in and around tumors. While some T cells are able to kill cancer cells, tumors can trick the immune cells through the microenvironment, according to the study.

Included in the study were biopsies from 73 patients with non-small cell lung cancer. The authors investigated 40 types of immune cells in the tissue samples.

The authors noted that the biopsies were composed of many noncancerous cells, with more than 65% being comprised of immune cells, according to the study.

“When we think about a tumor, we usually think about the accumulation of tumor cells,” said researcher Julia Kargl, PhD. “But when we look at these tumors, we have these islands of tumor cells and they are surrounded by immune cells. So, there’s a really strong immune reaction to the tumor, but the reaction just hasn’t been the right one to kill the tumor cells.”

The accumulation of noncancerous cells was largely made of neutrophils, which is the first responder to infections. While these immune cells normally live for 6 hours, the lung tumors kept them alive much longer and attracted new cells, according to the study.

The authors found that this forms a bubble around the tumor cells to prevent other immune cells from attacking the cancer.

Previous research showed that patients with few T cells in their tumors were less likely to respond to checkpoint inhibitors. This may be because there are less T cells for the drugs to “wake up,” according to the authors.

The researchers wrote that it is not clear what role neutrophils play in the tumor microenvironment. Additionally, they were unable to determine how immunotherapy could affect the cells, since the biopsies were taken during surgery.

They hypothesize that if neutrophils block other immune cells from entering the tumor, a drug that targets neutrophils could let other cells in and improve response to checkpoint inhibitors, according to the study. The authors are currently exploring the idea in mouse models of lung cancer.

“We are hoping that if we know which immune cells are present in the tumor, we could better identify patients that can benefit from immunotherapy,” Dr Kargl said. “We will need good criteria to select which drugs or which drug combination is beneficial for patients.”