Targeting Immunotherapy to the Tumor Microenvironment

Abstract

Targeting drugs to the tumor microenvironment has long been appreciated as a means of increasing local concentrations and decreasing systemic toxicities. How drug targeting might apply to immune-based therapies is less clear. In this review, we explain the immunology of cancer, with a focus on the principles of in situ vaccination. Certain types of therapies are more amenable to local versus systemic delivery; these include cytokines, adjuvants, radiation, and agents targeting tumor-resident cell populations. Several approaches for targeting the tumor microenvironment are under development. Nanoparticles, peptide or antibody-based delivery, and exploitation of cellular influx are all promising ways to delivery immune modulating compounds to tumors. J. Cell. Biochem. 118: 3049-3054, 2017. © 2017 Wiley Periodicals, Inc.

APRIL and BAFF increase breast cancer cell stemness

“…Additionally, they provide evidence for a new possible mechanism of therapy resistance that involves increased stemness by high APRIL levels as a result of the accumulation of androgen that could occur in aromatase inhibitors treated patients. They further provide evidence that, in order to establish optimal personalized, immune-related therapies in breast cancer patients, one should, in addition to the targeting of the stroma and cancer-infiltrating immune cells 8 , also investigate and target tumor cells, as was recently reported for another member of the TNFRSF, TNFR2 10,11 .…”

“…However, established immune-related therapies target immune cells (resident or infiltrating the tumor stroma) 8 , leading to an immune checkpoint blockade 9 , while the notion of immune-related properties of the cancer cell per se and its possible regulation as a possible therapeutic target is less well defined 10,11 .…”

“…A number of immune-related molecules are involved in the above mentioned interactions and being targeted in tumor immunotherapy approcahes. Among them, TNF superfamily members (including TNF, FAS and TRAIL and their receptors) 8 , have been actively investigated and targeted in a number of malignancies. The TNF superfamily includes 19 different ligands and 29 receptors, controls cell survival and differentiation and plays an important role in the growth, organization, and homeostasis of different tissues, by modulating major signaling pathways 12 .…”

SARI suppresses colitis‐associated cancer development by maintaining MCP‐1‐mediated tumour‐associated macrophage recruitment

“…It is widely acknowledged that tumour microenvironment is an important regulator during tumour initiation, progression and metastasis . Thus, imaging and shaping tumour microenvironment are a potential strategy for improving immunotherapy effect, drug delivery and chemo‐sensitivity …”

“…3,4 Thus, imaging and shaping tumour microenvironment are a potential strategy for improving immunotherapy effect, drug delivery and chemo-sensitivity. [5][6][7] Inflammatory cells are a key component of the tumour microenvironment, and macrophages are present in almost all tumours.…”