Abstract
The microbiota plays a key role in regulating the innate and adaptive immune system. Herein, we review the immunological aspects of the microbiota in tumor immunity in mice and man, with a focus on toll-like receptor (TLR) agonists, vaccines, checkpoint modulators, chemotherapy, and adoptive T cell transfer (ACT) therapies. We propose innovative treatments that may safely harness the microbiota to enhance T cell-based therapies in cancer patients. Finally, we highlight recent developments in tumor immunotherapy, particularly novel ways to modulate the microbiome and memory T cell responses to human malignancies.
Highlights
Mammals have over 100 trillion microbes in distinct locations of the body-outnumbering mammalian cells 10-fold
Follow-up work by the Restifo lab revealed that depletion of lymphocytes that act as cytokine sinks alone, removal of regulatory T cells alone, or activation of the innate immune system via TLR4 signaling alone could not augment adoptive T cell transfer (ACT) in nonirradiated mice with melanoma [6]
The potent adjuvant functions of toll-like receptor (TLR) have been thoroughly investigated for cancer therapies, but the vast amount of data that has accumulated reveals that in oncological settings these therapies lack robust long-term efficacy
Summary
Mammals have over 100 trillion microbes in distinct locations of the body-outnumbering mammalian cells 10-fold. 1000 different types of microbes colonize the host. Healthy individuals differ vastly in the type of microbes that colonize their gut, likely as a consequence of their exposure to microorganisms after birth, genetics, environmental cues, and diet. These diverse microbial communities are collectively referred to as the microbiota [1]. Mutualistic microbes that colonize the gut are crucial for health These microbes sustain basic physiological processes—digestion, vitamin synthesis, and host-defense [3,4,5]. It is vital to understand the impact of these treatments on host-microbes and the immune system [9]
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