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22IN TARGETING THE HOST IN TNBC
G. Curigliano
Medicine, Istituto Europeo di Oncologia, Milano, ITALY
Cancer medicine is increasingly moving toward a new era of personalized
therapeutics that embraces integrative approaches. Combinatorial strategies will target
not only cancer cell-intrinsic pathways, but also cancer cell-extrinsic cells, pathways,
and mediators of the tumor microenvironment. As the strategic goal of defining the
roles of the tumor microenvironment in primary and metastatic tumor progression,
new discoveries can be envisioned to produce innovative multitargeting strategies that
will be able to more thoroughly extinguish primary and metastatic disease,
overcoming adaptive resistance mechanisms to such therapies. The cancer
microenvironment is constituted of non-transformed host stromal cells such as
endothelial cells,fibroblasts, various immune cells, and a complex extracellular matrix
secreted by both the normal and neoplastic cells embedded in it. The importance of
the microenvironment and its potential in cancer therapy is just being established.
Among modalities that target the microenvironment, harnessing immune responses
Annals of Oncology
has long been pursued. Efforts to turn on the immune system against cancers with
inactivated tumor vaccines or intratumor injections of bacterial products to induce
local inflammation and recruit an antitumor immune response have led to anecdotal
successes. A major limitation of the various approaches to turning on an immune
response to cancer is that the immune system exerts a major effort to avoid
immune over-activation, which could harm healthy tissues. Cancer takes
advantage of this ability to hide from the immune system by exploiting a series of
immune escape mechanisms that were developed to avoid autoimmunity
(mechanisms of tolerance). Among these mechanisms are the hijacking of
immune-cell–intrinsic checkpoints that are induced on T-cell activation. Blockade
of one of these checkpoints, cytotoxic T-lymphocyte–associated antigen 4
(CTLA-4) or the programmed death 1 (PD-1) receptor, provided the first evidence
of activity of an immune-modulation approach in the treatment of a solid tumor.
The future frontier in the treatment of cancer requires identification of potential
targets in order to personalize therapies. The immune system remembers what it
targets, so once the system is correctly activated, it may mediate a durable tumor
response.
Disclosure: The author has declared no conflicts of interest.
ix30 | Abstracts Volume 23 | Supplement 9 | September 2012