Enhanctd t cell meduted anti-tumorimmunity is observed in b cell deficient mice

Shannon P. Hilchey, Corliss L. Newman, Benjamin M. Segal, Joseph D. Rosenblatt

Research output: Contribution to journalArticle

Abstract

The role of B cells in anti-tumor immunity is not well understood. Although immunoglobulins have been detected targeting tumor specific antigens in cancer patients, they do not appear to be protective. Several syngeneic murine tumor models have demonstrated the ability of B cells to inhibit T cell mediated anti-tumor immunity. We have analyzed the growth characteristics of three C57B1/6 tumor lines, EL4, B16 and MC38, in immunocompetent (ICM) and B cell deficient (BCDM) mice. EL4, a T cell lymphoma, grows progressively in ICM but grows and regresses in BCDM. EL4 cells transduced to express the human costimulatory molecule B7.1, EL4/B7.1, initially grow and then are rejected in 100% of both ICM and BCDM. B16, a melanoma, and B16/B7.1 grow progressively in both ICM and BCDM. MC38, a colon adenocarcinoma, grows progressively in ICM but regress spontaneously in BCDM. MC38/B7.1 cells also grow progressively in ICM, but are rejected in 100% of BCDM. Immunohistochemical staining for CD4 and CD8 positive cells of MC38 tumor sections from ICM or BCDM demonstrate increased T cell infiltration in BCDM tumors. We have measured CTL activity against parental tumor cells from splenocytes of ICM and BCDM inoculated with the B16 or MC38 cell lines. No CTL activity was detected in vitro against B16 cells from splenocytes harvested from either ICM or BCDM inoculated with parental B16 or B16/B7.1. We also failed to detect significant CTL activity from ICM inoculated with either parental MC38 or MC38/B7.1. Significant CTL activity was observed from BCDM inoculated with either MC38 or MC38/B7.1. Cytokine profiles from in vitro splenocyte-tumor co-cultures demonstrate that BCDM splenocytes secrete significantly higher levels of both IFNgamma and IL-12 in response to priming with parental MC38 tumors as compared to ICM. The addition of CD40(+/+) but not CD40(-/-) B cells to BCDM splenocyte-tumor co-cultures results in a 50% inhibition of IFN-gamma production suggesting a role for CD40 in B cell mediated inhibition of anti-tumor activity. Future experiments to assess the mechanism of spontaneous tumor regression in BCDM are ongoing. We hypothesize that B cells interfere with effective immune responses to tumors, perhaps through alterations in dendritic cell/T cell interactions and/or through skewing of T cell responses towards the Th2 differentiation pathway. B cell depletion may augment existing strategies designed to evoke an anti-tumor Thl response.

Original languageEnglish (US)
Pages (from-to)27a
JournalBlood
Volume96
Issue number11 PART I
StatePublished - Dec 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Hilchey, S. P., Newman, C. L., Segal, B. M., & Rosenblatt, J. D. (2000). Enhanctd t cell meduted anti-tumorimmunity is observed in b cell deficient mice. Blood, 96(11 PART I), 27a.