Mar 28, 2020

The Paradox of Cancer Immune Exclusion: Immune Oncology Next Frontier

Cancer Treatment and Research
Sara I PaiFrancesco M Marincola

Abstract

Checkpoint inhibitor therapy (CIT) has revolutionized cancer treatment but it has also reached a standstill when an absent dialog between cancer and immune cells makes it irrelevant. This occurs with high prevalence in the context of "immune silent" and, even perhaps, "immune-excluded" tumors. The latter are characterized by T cells restricted to the periphery of cancer nests. Since in either case T cells do not come in direct contact with most cancer cells, CIT rests immaterial. Adoptive cell therapy (ACT), may also be affected by limited access to antigen-bearing cancer cells. While lack of immunogenicity intuitively explains the immune silent phenotype, immune exclusion is perplexing. The presence of T cells at the periphery suggests that chemo-attraction recruits them and an immunogenic stimulus promotes their persistence. However, what stops the T cells from infiltrating the tumors' nests and reaching the germinal center (GC)? Possibly, a concentric gradient of increased chemo-repulsion or decreased chemo-attraction demarcates an abrupt "do not trespass" warning. Various hypotheses suggest physical or functional barriers but no definitive consensus exists over the weight that each plays in human cancers. On one hand, it co...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Immune System
Malignant Neoplasms
Regulation of Direction of Cell Growth
Attractant
Intuition
Tumor Cells, Malignant
Stromal Cells
Cell Death
Immune Effector Cell
Peripheral

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

© 2020 Meta ULC. All rights reserved