Tumor immunology and cancer immunotherapy: summary of the 2014 SITC primer
Page et al. Journal for ImmunoTherapy of Cancer
Tumor immunology and cancer immunotherapy: summary of the 2014 SITC primer
David B. Page 0
Ariel Bulua Bourla 0
Anthony Daniyan 0
Jarushka Naidoo 0
Eric Smith 0
Melody Smith 0
Claire Friedman 0
Danny N. Khalil 0
Samuel Funt 0
Alexander N. Shoushtari 0
Willem W. Overwijk 1
Padmanee Sharma 1
Margaret K. Callahan 0
0 Memorial Sloan Kettering Cancer Center , 300 E 66th Street, BAIC 813, NY 10065 New York , USA
1 MD Anderson Cancer Center , Houston, TX , USA
The pioneers of tumor immunology and cancer immunotherapy, including the late William B. Coley and Lloyd J. Old, have championed the potential for immunotherapy for over a century. Finally, advances in our understanding of the fundamentals of tumor immunology are translating into clinical success, with recent US Food and Drug Administration approval of several immunotherapies that improve clinical outcomes across prostate cancer, metastatic melanoma, non-small cell lung cancer and lymphocytic leukemia. In tandem with these clinical successes, new technologies such as high-throughput DNA/RNA sequencing, genetic engineering, and streamlined ex vivo cell culturing have paved the way for the next generation of immunotherapies and provided new tools for investigating potential biomarkers of response to existing therapies. During the November 2014 Annual Meeting of the Society of the Immunotherapy of Cancer, leaders in tumor immunology and cancer immunotherapy convened at the second annual SITC Primer to review both current knowledge and future directions in the field. Here, we will review the key discussions across a variety of topics, including innate immunity, adaptive immunity, dendritic cells, adoptive T cell therapy, anti-tumor antibodies, cancer vaccines, immune checkpoint blockade, challenges to immunotherapy, monitoring immune responses, and immunotherapy clinical trial design.
CTLA4; PD-1; PD-L1; Melanoma; Prostate cancer; Kidney cancer; Bladder cancer; Lung cancer; Vaccine; Adoptive therapy; Nivolumab; Ipilimumab; Pembrolizumab; SITC; Primer
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Introduction
Clinical immunotherapy is undergoing a renaissance, with
recent rapid-fire US Food and Drug Association (FDA)
approval of numerous immunotherapies across several tumor
types, including ipilimumab, pembrolizumab and
nivolumab for metastatic melanoma, nivolumab for non-small
cell squamous cell lung cancer, sipuleucel-T for prostate
cancer, and blinatumomab for acute lymphocytic leukemia
(ALL). In parallel, advances in research tools for basic and
translational investigation have afforded an enhanced
understanding of the fundamentals of tumor immunology,
laying the foundation for subsequent development of the
next generation of immunotherapeutic approaches. These
approaches include therapeutic antibodies against novel
targets, adoptive T-cell therapies, tumor vaccines,
bispecific antibody constructs, and combination therapies. In
November 2014, the Society for Immunotherapy of
Cancer (SITC) held the second annual Primer on Tumor
Immunology and Cancer Immunotherapy, organized by
Drs. Willem W. Overwijk and Padmanee Sharma. In this
review, we will summarize the key topics presented by the
faculty, focusing upon recent advances in the field of
immunotherapy. This year’s faculty included Dr. Vincenzo
Bronte, MD (innate immunity), Dr. Lisa H. Butterfield,
PhD (dendritic cells), Dr. Jonathan Powell, MD/PhD
(adaptive immunity), Dr. Carl H. June, MD (adoptive
T-cell therapy), Dr. Sattva S. Neelapu, MD (anti-tumor
antibodies), Dr. Margaret K. Callahan, MD/PhD (obstacles
to driving an immune response), Dr. Willem W. Overwijk,
PhD (cancer vaccines), Dr. James P. Allison, PhD
(targeting immune checkpoints in cancer therapy), Dr. Sasha
Gnjatic, PhD (immune monitoring), and Dr. Padmanee
Sharma, MD/PhD (pre-surgical clinical trial design).
Innate immunity
The innate immune system is evolutionarily conserved
across both vertebrates and non-vertebrates, and provides
a rapid, but non-specific, protective immune response to
invading pathogens, The innate immune system responds
within minutes and does not generate memory, but
notably can stimulate and shape long-lasting antigen-specific
immunity through a variety of mechanisms. Principal
components of innate immunity include epithelial
barriers (skin and mucosal membranes), pattern recognition
receptors (PRRs), effector cells (monocytes/macrophages,
natural killer (NK) cells, dendritic cells (DCs), mast cells,
neutrophils, innate lymphoid cells, and eosinophils among
others) and humoral components (complement proteins
and collectins).
The innate immune response can be initiated through
activation of PRRs such as Toll-like receptors (TLR).
These receptors can be extracellular, cytosolic, or
endosomal. Pathogen associated molecular patterns (PAMP)
are molecules shared by groups of pathogens (i.e. gram
positive and gram negative bacteria), are not present in
mammalian cells, and are capable of binding PRRs. These
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