eLife: Cancer cells can form temporary structures that evade immunotherapy

The findings, published in the journal eLife, provide a new theory
of how tumor cells can avoid being destroyed by the immune system.

"Cancer immunotherapy uses the body's immune system to fight cancer
.

To determine how tumors recur after immunotherapy, Carmi and his team first compared the genome-wide genome sequences
of primary and recurrent tumors in the same patient.

Next, the team studied the process in breast cancer and melanoma, using a mouse model
of immunotherapy-resistant tumor recurrence.

To better describe the tumor cells that survived in mice after immunotherapy, the researchers isolated and studied live tumor cells
.

To prove that this result is not due to the isolation of melanoma cells, the team also analyzed tumors with fluorescently labeled nuclei and cell membranes
.

The team next tested whether this phenomenon could occur in
human cancer.

Finally, they examined the clinical relevance of this finding by analyzing the cancerous tissue of multiple organs in four patients with stage 4 melanoma
.

Yaron Carmi, lead researcher and senior author of the Department of Pathology at Tel Aviv University's Sackler School of Medicine, said: "This previously unknown mechanism of tumor resistance highlights the limitations
of current immunotherapy.
" "Over the past decade, many clinical studies have used immunotherapy, followed by chemotherapy
.
But our findings suggest that while immunotherapy is being conducted, there is a need for timed suppression of relevant signaling pathways to prevent tumors from becoming resistant to subsequent treatments
.
”

essay

Transient cell-in-cell formation underlies tumor relapse and resistance to immunotherapy