Analysis of cancer cell-intrinsic immune regulation in response to CD8+ T cell attack.

Immunotherapies against cancer continue to improve, but many cancers show primary or secondary resistance. Novel research strategies are necessary to reach a comprehensive understanding of the underlying mechanisms. There is increasing evidence that T cells themselves provoke immune escape of cancer cells.

T cell-induced CSF1 promotes melanoma resistance to PD1 blockade.

Colony-stimulating factor 1 (CSF1) is a key regulator of monocyte/macrophage differentiation that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). We show that CSF1 is expressed in human melanoma, and patients with metastatic melanoma have increased CSF1 in blood compared to healthy subjects. In tumors, CSF1 expression correlated with the abundance of CD8 T cells and CD163 TAMs.

Broad and Conserved Immune Regulation by Genetically Heterogeneous Melanoma Cells.

Although mutations drive cancer, it is less clear to what extent genetic defects control immune mechanisms and confer resistance to T-cell-based immunotherapy. Here, we studied the reactions of malignant and benign melanocyte lines to cytotoxic CD8 T cells (CTL) using flow cytometry and gene expression analyses. We found rapid and broad upregulation of immune-regulatory genes, essentially triggered by CTL-derived IFNγ and augmented by TNFα.

A Well-Controlled Experimental System to Study Interactions of Cytotoxic T Lymphocytes with Tumor Cells.

While T cell-based immunotherapies are steadily improving, there are still many patients who progress, despite T cell-infiltrated tumors. Emerging evidence suggests that T cells themselves may provoke immune escape of cancer cells. Here, we describe a well-controlled co-culture system for studying the dynamic T cell - cancer cell interplay, using human melanoma as a model.

TetraMabs: simultaneous targeting of four oncogenic receptor tyrosine kinases for tumor growth inhibition in heterogeneous tumor cell populations.

Monoclonal antibody-based targeted tumor therapy has greatly improved treatment options for patients. Antibodies against oncogenic receptor tyrosine kinases (RTKs), especially the ErbB receptor family, are prominent examples. However, long-term efficacy of such antibodies is limited by resistance mechanisms.

Inhibitory Receptors Beyond T Cell Exhaustion.

Inhibitory receptors (iRs) are frequently associated with "T cell exhaustion". However, the expression of iRs is also dependent on T cell differentiation and activation. Therapeutic blockade of various iRs, also referred to as "checkpoint blockade", is showing -unprecedented results in the treatment of cancer patients.