SIRPα expression delineates subsets of intratumoral monocyte/macrophages with different functional and prognostic impact in follicular lymphoma

Ya Ping Chen, Hyo Jin Kim, Hongyan Wu, Tammy Price-Troska, Jose C. Villasboas, Shahrzad Jalali, Andrew L. Feldman, Anne J. Novak, Zhi Zhang Yang, Stephen M. Ansell

Research output: Contribution to journalArticle

Abstract

Signal regulatory protein-α (SIRPα) is a key member of the “do-not-eat-me” signaling pathway, but its biological role and clinical relevance in B-cell NHL is relatively unknown. Using biopsy specimens from follicular lymphoma (FL), we identified three subsets (CD14+SIRPαhi, CD14SIRPαlow, and CD14SIRPαneg) of monocyte/macrophages (Mo/MΦ) based on CD14 and SIRPα expression. CD14+SIRPαhi cells expressed common Mo/MΦ markers; exhibited characteristic differentiation, migration, and phagocytosis; and suppressed T-cell function. CD14SIRPαlow cells expressed fewer typical Mo/MΦ markers; migrated less and phagocytosed tumor cells less efficiently; and stimulated rather than suppressed T-cell function. Interestingly, the CD14SIRPαneg subset expressed distinct Mo/MΦ markers compared to the other two subsets; had limited ability to migrate and phagocytose; but stimulated T-cell function. When using SIRPα-Fc to block the interaction between SIRPα and CD47, alone or in combination with rituximab, phagocytosis of tumor cells was differentially increased in the three Mo/MΦ subsets. Clinically, increased numbers of CD14+SIRPαhi cells were associated with an inferior survival in FL. In contrast, increased numbers of the CD14SIRPαlow subset appeared to correlate with a better survival. Taken together, our results show that SIRPα expression delineates unique subsets of intratumoral Mo/MΦs with differing prognostic importance.

Original languageEnglish (US)
Article number84
JournalBlood cancer journal
Volume9
Issue number10
DOIs
StatePublished - Oct 1 2019

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Follicular Lymphoma
Monocytes
Macrophages
Cytophagocytosis
Proteins
T-Lymphocytes
Phagocytosis
Neoplasms
B-Lymphocytes
Biopsy

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

SIRPα expression delineates subsets of intratumoral monocyte/macrophages with different functional and prognostic impact in follicular lymphoma. / Chen, Ya Ping; Kim, Hyo Jin; Wu, Hongyan; Price-Troska, Tammy; Villasboas, Jose C.; Jalali, Shahrzad; Feldman, Andrew L.; Novak, Anne J.; Yang, Zhi Zhang; Ansell, Stephen M.

In: Blood cancer journal, Vol. 9, No. 10, 84, 01.10.2019.

Research output: Contribution to journalArticle

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abstract = "Signal regulatory protein-α (SIRPα) is a key member of the “do-not-eat-me” signaling pathway, but its biological role and clinical relevance in B-cell NHL is relatively unknown. Using biopsy specimens from follicular lymphoma (FL), we identified three subsets (CD14+SIRPαhi, CD14−SIRPαlow, and CD14−SIRPαneg) of monocyte/macrophages (Mo/MΦ) based on CD14 and SIRPα expression. CD14+SIRPαhi cells expressed common Mo/MΦ markers; exhibited characteristic differentiation, migration, and phagocytosis; and suppressed T-cell function. CD14−SIRPαlow cells expressed fewer typical Mo/MΦ markers; migrated less and phagocytosed tumor cells less efficiently; and stimulated rather than suppressed T-cell function. Interestingly, the CD14−SIRPαneg subset expressed distinct Mo/MΦ markers compared to the other two subsets; had limited ability to migrate and phagocytose; but stimulated T-cell function. When using SIRPα-Fc to block the interaction between SIRPα and CD47, alone or in combination with rituximab, phagocytosis of tumor cells was differentially increased in the three Mo/MΦ subsets. Clinically, increased numbers of CD14+SIRPαhi cells were associated with an inferior survival in FL. In contrast, increased numbers of the CD14−SIRPαlow subset appeared to correlate with a better survival. Taken together, our results show that SIRPα expression delineates unique subsets of intratumoral Mo/MΦs with differing prognostic importance.",
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AU - Jalali, Shahrzad

AU - Feldman, Andrew L.

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