Researchers from University of Pennsylvania School of Medicine reveal that immunotherapy sensitivity of tumors is controlled by factors specific to individual cancer cells.
The ‘hot’ tumor cells filled with T cells are highly sensitive to immunotherapy than the ’cold’ tumor cells with fewer T cells. A team of researchers from Penn Medicine’s Abramson Cancer Center (ACC) discovered that immunotherapy sensitivity is determined controlled by factors specific to individual cancer cells. Tumors need to evade the immune system to grow. This is done by developing as a cold tumor with a limited number of T cells, and as a hot tumor by exhausting the T cells. Both the processes are effective in shielding tumor cells from destruction by the immune system. Pancreatic tumors are especially known to span the spectrum of T cell infiltration. The researchers created an array of pancreatic tumor cell lines derived from a mouse model. The array was implanted in normal mice with a functioning immune system. It developed into tumors of hot and cold categories. The hot tumors were emerged as the dominant type. Tumor regressions were evident in half of the mice with hot tumors after dosing them with a checkpoint blockade drug. The effects further enhanced with the addition of an anti-CD40 agonist. The mice with hot tumors with a combination of chemo- and immunotherapy called GAFCP survived for a period of 6 months. However, the mice with cold tumors fell pray to their cancer following this therapy. The research was published in the journal Immunity on June 26, 2018.
The researchers analyzed the for factors released by cold tumors that attracted myeloid cells to reveal that these cold tumors make a compound called CXCL1, responsible for signaling the myeloid cells to enter tumors and restrict the T cells. This leads to insensitivity to immunotherapy. However, eliminating CXCL1 in cold tumors led to T cell infiltration and sensitivity to immunotherapy. The array of cell lines created by the researchers imitate a spectrum of pancreatic tumor features, which could help to further identify and develop therapies for specific subsets of patients with various states of tumor heterogeneity.