Tumor microenvironment (TME)-driven immune suppression in B cell malignancy

TY - JOUR

T1 - Tumor microenvironment (TME)-driven immune suppression in B cell malignancy

AU - Nicholas, Nicole S.

AU - Apollonio, Benedetta

AU - Ramsay, Alan G.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Immune checkpoint blockade antibodies and immunomodulatory drugs can unleash anti-tumor T cell immunity and mediate durable cancer regressions. However, only a fraction of patients currently respond to immunotherapy. Lymphoid malignancies are known to have clinically exploitable immune sensitivity and their intrinsic lymphoid tumor-microenvironment (TME) should make them natural targets for immunotherapy. However, accumulating evidence is showing that malignant cells engage in novel associations/interdependencies with reprogrammed immune and stromal cells in the TME that provide crucial contributions to the licencing of tumour progression and immune evasion (suppression of antitumor immune responses). In this review, we outline TME-driven contributions to the licencing of immune evasion mechanisms including the expression and activity of the immune checkpoint network, focussing on two types of B cell malignancy: indolent chronic lymphocytic leukemia (CLL) and aggressive diffuse large B-cell lymphoma (DLBCL). We also highlight recent therapeutic strategies to re-educate the TME to have anti-tumorigenic effects. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

AB - Immune checkpoint blockade antibodies and immunomodulatory drugs can unleash anti-tumor T cell immunity and mediate durable cancer regressions. However, only a fraction of patients currently respond to immunotherapy. Lymphoid malignancies are known to have clinically exploitable immune sensitivity and their intrinsic lymphoid tumor-microenvironment (TME) should make them natural targets for immunotherapy. However, accumulating evidence is showing that malignant cells engage in novel associations/interdependencies with reprogrammed immune and stromal cells in the TME that provide crucial contributions to the licencing of tumour progression and immune evasion (suppression of antitumor immune responses). In this review, we outline TME-driven contributions to the licencing of immune evasion mechanisms including the expression and activity of the immune checkpoint network, focussing on two types of B cell malignancy: indolent chronic lymphocytic leukemia (CLL) and aggressive diffuse large B-cell lymphoma (DLBCL). We also highlight recent therapeutic strategies to re-educate the TME to have anti-tumorigenic effects. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

KW - CLL

KW - CTLA-4

KW - DLBCL

KW - Immune checkpoint blockade

KW - Immune evasion

KW - Lenalidomide

KW - PD-1

KW - PD-L1

KW - T cells

UR - http://www.scopus.com/inward/record.url?scp=84955209668&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2015.11.003

DO - 10.1016/j.bbamcr.2015.11.003

M3 - Article

AN - SCOPUS:84955209668

SN - 0167-4889

VL - 1863

SP - 471

EP - 482

JO - Biochimica et biophysica acta-Molecular cell research

JF - Biochimica et biophysica acta-Molecular cell research

IS - 3

ER -