Mechanisms regulating immune surveillance of cellular stress in cancer

Abstract

The purpose of this review is to explore immune-mediated mechanisms of stress surveillance in cancer, with particular emphasis on the idea that all cancers have classical hallmarks (Hanahan and Weinberg in Cell 100:57-70, 67; Cell 144:646-674, 68) that could be interrelated. We postulate that hallmarks of cancer associated with cellular stress pathways (Luo et al. in Cell 136:823-837, 101) including oxidative stress, proteotoxic stress, mitotic stress, DNA damage, and metabolic stress could define and modulate the inflammatory component of cancer. As such, the overarching goal of this review is to define the types of cellular stress that cancer cells undergo, and then to explore mechanisms by which immune cells recognize, respond to, and are affected by each stress response.

Keywords: Cancer immune surveillance; Cancer immunity; Cancer inflammation; Cancer-associated stress; Chromosome instability (CIN); DNA damage response (DDR); Danger-associated molecular patterns (DAMPs); ER stress; Hyperploidy; Immunogenic cell death; Mitochondrial stress; Oncometabolites; Senescence-associated secretory phenotype (SASP); Tumor microenvironment; Unfolded protein response.

Fig. 1

Regulation of immune surveillance by intrinsic stress pathways in cancer. Shown are the five unique stress pathways that occur in cancer cells (inner circle) and the effects of each stress on immunity (outer circle). These effects are broad reaching and can promote (red font) and/or inhibit (blue font) anti-tumor immunity, or both (black font). Adapted from Luo et al. [101]

Fig. 2

Interrelation of stress pathways. The five stress pathways that occur in cancer cells are highly interrelated and can each directly cause at least one or more other stress response. The arrows demonstrate direct (rather than indirect) interconnections between each of the five stress pathways, and the text next to each arrow describes how each direct effect is mediated