1 research outputs found
Complementing the cancer-immunity cycle
Reactivation of cytotoxic CD8+ T-cell responses has set a new direction for cancer
immunotherapy. Neutralizing antibodies targeting immune checkpoint programmed cell
death protein 1 (PD-1) or its ligand (PD-L1) have been particularly successful for tumor
types with limited therapeutic options such as melanoma and lung cancer. However,
reactivation of T cells is only one step toward tumor elimination, and a substantial fraction
of patients fails to respond to these therapies. In this context, combination therapies
targeting more than one of the steps of the cancer-immune cycle may provide significant
benefits. To find the best combinations, it is of upmost importance to understand the
interplay between cancer cells and all the components of the immune response. This
review focuses on the elements of the complement system that come into play in the
cancer-immunity cycle. The complement system, an essential part of innate immunity,
has emerged as a major regulator of cancer immunity. Complement effectors such
as C1q, anaphylatoxins C3a and C5a, and their receptors C3aR and C5aR1, have
been associated with tolerogenic cell death and inhibition of antitumor T-cell responses
through the recruitment and/or activation of immunosuppressive cell subpopulations
such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), or M2
tumor-associated macrophages (TAMs). Evidence is provided to support the idea that
complement blocks many of the effector routes associated with the cancer-immunity
cycle, providing the rationale for new therapeutic combinations aimed to enhance the
antitumor efficacy of anti-PD-1/PD-L1 checkpoint inhibitors