New Insight into Blood Cancer's Evasion Strategy: The 'Cell-in-Cell' Mechanism in Bone Marrow

Recent research from Fox Chase Cancer Center has uncovered a novel survival tactic employed by blood cancer cells, specifically chronic lymphocytic leukemia (CLL) cells, to evade treatment. This mechanism, termed "cell-in-cell," involves cancer cells entering and residing within bone marrow fibroblasts—cells that typically support tissue structure and healing. The groundbreaking study, published in the journal Blood Neoplasia, reveals that cancer cells utilize this hidden refuge to survive anti-cancer drugs, potentially leading to residual disease and relapse even after initial therapy success.

This five-year investigation, led by Dr. Y. Lynn Wang, highlighted how CLL cells respond to BTK inhibitors—common targeted therapies—by increasing CXCR4 receptor expression. This receptor guides the cancer cells towards fibroblasts, where they are engulfed and shielded from treatment. Inside these supporting cells, the cancer cells maintain their viability, protected from drug effects. Live imaging techniques confirmed that these internalized cells not only survive but also exhibit higher resistance to therapy compared to those remaining outside fibroblasts.

The researchers demonstrated that blocking CXCR4 receptors prevents cancer cells from entering fibroblasts, rendering them more susceptible to treatment. This approach could be combined with existing therapies, such as BTK inhibitors, to enhance complete remission rates. Beyond CLL, this "cell-in-cell" behavior was also observed in follicular lymphoma, indicating that this escape strategy might be widespread among various cancer types.

Understanding this hidden niche opens new avenues for therapeutic intervention. By targeting the mechanisms that allow tumor cells to retreat into safe environments within the bone marrow, clinicians may be able to reduce residual disease and improve long-term outcomes for patients. The findings underscore the importance of developing combination strategies that can disrupt these survival tactics and move closer to effective cancer eradication.