Changes in the local tumor microenvironment in recurrent cancers may explain the failure of vaccines after surgery

Jarrod Predina, Evgeniy Eruslanov, Brendan Judy, Veena Kapoor, Guanjun Cheng, Liang Chuan Wang, Jing Sun, Edmund K. Moon, Zvi Gregorio Fridlender, Steven Albelda, Unil Singhal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Each year, more than 700,000 people undergo cancer surgery in the United States. However, more than 40% of those patients develop recurrences and have a poor outcome. Traditionally, the medical community has assumed that recurrent tumors arise from selected tumor clones that are refractory to therapy. However, we found that tumor cells have few phenotypical differences after surgery. Thus, we propose an alternative explanation for the resistance of recurrent tumors. Surgery promotes inhibitory factors that allow lingering immunosuppressive cells to repopulate small pockets of residual disease quickly. Recurrent tumors and draining lymph nodes are infiltrated with M2 (CD11b +F4/80hiCD206hi and CD11b+F4/80 hiCD124hi) macrophages and CD4+Foxp3 + regulatory T cells. This complex network of immunosuppression in the surrounding tumor microenvironment explains the resistance of tumor recurrences to conventional cancer vaccines despite small tumor size, an intact antitumor immune response, and unaltered cancer cells. Therapeutic strategies coupling antitumor agents with inhibition of immunosuppressive cells potentially could impact the outcomes of more than 250,000 people each year.

Original languageAmerican English
Pages (from-to)E415-E424
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number5
DOIs
StatePublished - 29 Jan 2013
Externally publishedYes

Keywords

  • Immunology
  • T regulatory cells
  • Tumor macrophages

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