Characterization of effusion-infiltrating T cells: benign versus malignant effusions.
OBJECTIVE
While naïve T cells circulate between peripheral blood and lymph nodes, memory effector T cells acquire certain surface molecules that enable them to travel to peripheral tissues and exert their effector function. We analyzed whether deficient numbers of effector-type T cells within the malignant effusion might contribute to tumor escape from immunosurveillance.


METHODS
We analyzed the expression of a broad range of adhesion molecules and chemokine receptors (CD62L, CD56, CCR4, CCR5, CCR7, CXCR3, CLA, and integrin alpha 4 beta 7) on tumor-associated lymphocytes in effusions and peripheral blood lymphocytes of patients with malignant ascites (n = 11) or malignant pleural effusion (n = 16). A tumor-associated lymphocyte:peripheral blood lymphocyte ratio was calculated as an indicator for homing of lymphocytes into the effusions and was compared with patients with nonmalignant ascites (n = 17).


RESULTS
Patients with malignancies show an increased enrichment of T cells expressing the phenotype of "naïve" (CD62L+ and CD45RA+CCR7+), "central memory" (CD45RA-CCR7+), and type 2-polarized (CCR4+) T cells within their effusions. In contrast, enrichment of "effector"-type (CD45RA-CCR7- or CD45RA+CCR7-) and presumably type 1-polarized T cells (CCR5+) at the tumor site is deficient. The same is true for natural killer cells and potentially cytotoxic CD56+ T cells.


CONCLUSIONS
Here we show for the first time that patients with malignant effusions show a deficient enrichment of T cells expressing the phenotype of type-1-polarized effector T cells at the tumor site. This mechanism is likely to contribute to the escape of tumor cells from immunosurveillance.
Atanackovic
Djordje
D
Oncology/Hematology, Department of Medicine, University Hospital Eppendorf, Hamburg, Germany. D.Atanackovic@uke.uni-hamburg.de
Block
Andreas
A
de Weerth
Andreas
A
Faltz
Christiane
C
Hossfeld
Dieter Kurt
DK
Hegewisch-Becker
Susanna
S
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005355:Fibrosis; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets; D013601:T-Lymphocytes / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D019707:Receptors, Chemokine; D015375:Receptors, Interleukin-2; C054979:antigen T cell receptor, zeta chain