B Cells in Solid Tumors: Their Role in Tumor Pathogenesis and Antitumor Immunity

Abstract Diagnosis of meningeal localization of lymphoid malignancies by means of cytologic examination of the cerebrospinal fluid (CSF) can be difficult. Thus far no reliable CSF tumor markers have been identified. CD27 is a transmembrane disulfide-linked 55-kD homodimer present on most peripheral blood T cells and on a subset of B cells. CD27 is also expressed on human malignant B cells and high levels of soluble CD27 can be present in the serum of patients with B-cell malignancies. The aim of this study is to determine prospectively the diagnostic value of CSF sCD27 as a tumor marker in patients with meningeal localization of lymphoid malignancies. CSF sCD27 levels were determined by sandwich enzyme-linked immunosorbent assay. The optimal cut-off value using receiver operator characteristics curves was found to be 10 U/mL. sCD27 levels were normal in all 50 control patients (lumbar disc protrusion) and in 39 of 40 samples obtained from patients with either solid tumors or acute myeloid leukemia. Of 104 CSF samples from 70 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) undergoing routine central nervous system (CNS) staging, sCD27 was false positive and false negative in only one sample each. In 70 samples from 45 patients suspected of meningeal localization of ALL or NHL, the sCD27 test had an excellent sensitivity (100%) and specificity (82%). In 7 patients with positive CSF studied longitudinally, sCD27 levels correlated very well with remission and relapse. sCD27 levels were not nonspecifically increased by the administration of cytostatic drugs. Finally, sCD27 was also elevated in the 4 patients studied with primary central nervous system lymphoma (PCNSL). CSF sCD27 is a promising tumor marker in patients with either meningeal localization of lymphoid malignancies or PCNSL, and can be useful in the differential diagnosis of CNS involvement by either lymphoid malignancies or solid tumors.

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Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy

eLife ◽

10.7554/elife.57243 ◽

2020 ◽

Vol 9 ◽

Author(s):

Richard Lee Barrett ◽

Ellen Puré

Keyword(s):

Solid Tumors ◽

Immune Cells ◽

Antitumor Immunity ◽

Critical Role ◽

Therapeutic Resistance ◽

Cancer Associated Fibroblasts ◽

Tissue Architecture ◽

Immunosuppressive Activity ◽

Major Mechanism ◽

And Function

Fibroblasts play an essential role in organogenesis and the integrity of tissue architecture and function. Growth in most solid tumors is dependent upon remodeling ‘stroma’, composed of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), which plays a critical role in tumor initiation, progression, metastasis, and therapeutic resistance. Recent studies have clearly established that the potent immunosuppressive activity of stroma is a major mechanism by which stroma can promote tumor progression and confer resistance to immune-based therapies. Herein, we review recent advances in identifying the stroma-dependent mechanisms that regulate cancer-associated inflammation and antitumor immunity, in particular, the interactions between fibroblasts and immune cells. We also review the potential mechanisms by which stroma can confer resistance to immune-based therapies for solid tumors and current advancements in stroma-targeted therapies.

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Elevation of cerebrospinal fluid soluble CD27 levels in patients with meningeal localization of lymphoid malignancies [published erratum appears in Blood 1996 Oct 1;88(7):2818]

Blood ◽

10.1182/blood.v87.5.1985.bloodjournal8751985 ◽

1996 ◽

Vol 87 (5) ◽

pp. 1985-1989

Author(s):

MJ Kersten ◽

LM Evers ◽

PL Dellemijn ◽

H van den Berg ◽

P Portegies ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

B Cells ◽

Tumor Marker ◽

Solid Tumors ◽

Enzyme Linked Immunosorbent Assay ◽

Disc Protrusion ◽

Cytologic Examination ◽

Lymphoid Malignancies

Diagnosis of meningeal localization of lymphoid malignancies by means of cytologic examination of the cerebrospinal fluid (CSF) can be difficult. Thus far no reliable CSF tumor markers have been identified. CD27 is a transmembrane disulfide-linked 55-kD homodimer present on most peripheral blood T cells and on a subset of B cells. CD27 is also expressed on human malignant B cells and high levels of soluble CD27 can be present in the serum of patients with B-cell malignancies. The aim of this study is to determine prospectively the diagnostic value of CSF sCD27 as a tumor marker in patients with meningeal localization of lymphoid malignancies. CSF sCD27 levels were determined by sandwich enzyme-linked immunosorbent assay. The optimal cut-off value using receiver operator characteristics curves was found to be 10 U/mL. sCD27 levels were normal in all 50 control patients (lumbar disc protrusion) and in 39 of 40 samples obtained from patients with either solid tumors or acute myeloid leukemia. Of 104 CSF samples from 70 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) undergoing routine central nervous system (CNS) staging, sCD27 was false positive and false negative in only one sample each. In 70 samples from 45 patients suspected of meningeal localization of ALL or NHL, the sCD27 test had an excellent sensitivity (100%) and specificity (82%). In 7 patients with positive CSF studied longitudinally, sCD27 levels correlated very well with remission and relapse. sCD27 levels were not nonspecifically increased by the administration of cytostatic drugs. Finally, sCD27 was also elevated in the 4 patients studied with primary central nervous system lymphoma (PCNSL). CSF sCD27 is a promising tumor marker in patients with either meningeal localization of lymphoid malignancies or PCNSL, and can be useful in the differential diagnosis of CNS involvement by either lymphoid malignancies or solid tumors.

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Abstract 1878: Fc-enhanced anti-CTLA-4 antibody, AGEN1181: new mechanistic insights for potent antitumor immunity and combination potential in treatment-resistant solid tumors

10.1158/1538-7445.am2021-1878 ◽

2021 ◽

Author(s):

Antoine J. Tanne ◽

Claire Galand ◽

Abdo Abou-Slaybi ◽

Margaret Wilkens ◽

Marilyn Marques ◽

...

Keyword(s):

Solid Tumors ◽

Antitumor Immunity ◽

Treatment Resistant

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Abstract 941: B cells are required to generate optimal antitumor immunity in response to PD-1 blockade treatment

10.1158/1538-7445.sabcs18-941 ◽

2019 ◽

Author(s):

Shubhra Singh ◽

Karishma Bavisi ◽

Jason Roszik ◽

Adi Diab ◽

Richard E. Davis ◽

...

Keyword(s):

B Cells ◽

Antitumor Immunity

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Pre-B-cells in normal human bone marrow and in bone marrow from patients with leukemia in remission: persistent quantitative differences and possible expression of cell surface IgM in vitro

Blood ◽

10.1182/blood.v61.3.464.464 ◽

1983 ◽

Vol 61 (3) ◽

pp. 464-468 ◽

Cited By ~ 10

Author(s):

ER Pearl

Keyword(s):

Bone Marrow ◽

B Cells ◽

Acute Leukemia ◽

B Cell ◽

Solid Tumors ◽

B Lymphocytes ◽

Lymphoid Cells ◽

Barr Virus ◽

Marrow Cells

Abstract Pre-B-cells are bone marrow lymphoid cells that lack surface immunoglobulin (sIg-) but contain intracytoplasmic (c) IgM heavy chains and are probably the immediate precursors of immature sIgM+ B lymphocytes. To better understand early stages of B-cell development, immunofluorescence techniques were employed to identify pre-B-cells and B lymphocytes and to examine the expression of sIgM in vitro by human marrow that had been previously depleted of B cells by immunoadsorption. Marrow was derived from patients with acute leukemia in long-term remission off therapy and from a variety of controls. The pre-B-cell compartment was greatly expanded in the marrow of leukemia remission patients for more than 2 yr following cessation of therapy. A similar finding was noted in two patients with lymphoma who had also completed chemotherapy, but not in three with solid tumors prior to therapy. sIgM+ B cells appeared in cultures of sIg- marrow cells from leukemia patients, but not the controls, and only after exposure to Epstein-Barr virus (EBV). At least some of the sIgM+ lymphocytes also expressed cIgM and were probably derived from pre-B-cells. The results of this study (A) confirm that patients who have completed treatment for acute leukemia have a prolonged elevation of pre-B-cell proportions, (B) demonstrate that similar abnormalities may exist in patients with certain solid tumors following chemotherapy, and (C) suggest that a fraction of sIg- human marrow cells, perhaps pre-B- cells, bear a receptor for EBV and can be induced to express to sIgM in vitro.

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