PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
Authors: Pranav Murthy; Chigozirim N Ekeke; Kira L Russell; Samuel C Butler; Yue Wang; James D Luketich; Adam C Soloff; Rajeev Dhupar; Michael T Lotze Journal: Oncoimmunology Date: 2019-01-22 Impact factor: 8.110
Authors: Regina Lin; Ling Chen; Gang Chen; Chunyan Hu; Shan Jiang; Jose Sevilla; Ying Wan; John H Sampson; Bo Zhu; Qi-Jing Li Journal: J Clin Invest Date: 2014-10-27 Impact factor: 14.808
Authors: Nicola Principe; Joel Kidman; Richard A Lake; Willem Joost Lesterhuis; Anna K Nowak; Alison M McDonnell; Jonathan Chee Journal: Front Oncol Date: 2021-04-27 Impact factor: 6.244