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Targeting the Tumor Microenvironment

  • Paolo Strati
  • Nathan H. FowlerEmail author
  • Eric Fountain
Chapter

Abstract

The complexity of the tumor microenvironment prior to the development of anti-CD20 therapy (e.g., rituximab) for follicular lymphoma has been well characterized. The presence of CD8+ tumor-infiltrating lymphocytes and regulatory T cells has been demonstrated to be associated with a more favorable prognosis. Macrophages expression, on the other hand, has been shown to contribute to tumor dissemination, with increased expression of the CD163+ M2 macrophage phenotype conferring a poor prognosis while promoting tumor angiogenesis . This negative prognostic effect of infiltrating macrophages in the pre-rituximab era was later confirmed through gene-expression profiling. The advent of rituximab, however, brought a new era of effective tumor destruction through antibody-dependent cell-mediated cytotoxicity (ADCC), which relies on the presence of Fc receptors on macrophages, natural killer cells, and neutrophils, in addition to direct apoptotic effects . Recent studies have shown evidence that the addition of rituximab reverses the negative prognostic effect of high tumor-associated macrophages within the microenvironment; an increased number of macrophages were associated with improved progression-free survival in those treated with R-CHOP but not CHOP, for example. Despite significant heterogeneity in macrophage subtype and function, this reversal in the prognostic effect of macrophages within the tumor microenvironment has been seen with both the CD163+ M2 macrophage phenotype and CD68+ macrophages, and confirmed most recently through gene expression profiling. This effect may be dependent upon the specifics of the concurrent chemotherapy regimen, however, as patients who receive a doxorubicin containing regimen were shown to have a 5-year PFS of 60% versus 44%, p = 0.01, in one study.

Keywords

Monoclonal antibodies Immunomodulatory drugs B-cell receptor (BCR) Immune checkpoint inhibitors Nivolumab Pembrolizumab Pidilizumab 

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Paolo Strati
    • 1
  • Nathan H. Fowler
    • 1
    Email author
  • Eric Fountain
    • 2
  1. 1.Department of Lymphoma/MyelomaThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Division of Cancer MedicineUniversity of Texas, MD AndersonHoustonUSA

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