Tetraspanin CD81 promotes tumor growth and metastasis by modulating the functions of T regulatory and myeloid-derived suppressor cells.
Tumor cells counteract innate and adaptive antitumor immune responses by recruiting regulatory T cells (Treg) and innate myeloid-derived suppressor cells (MDSC), which facilitate immune escape and metastatic dissemination. Here we report a role in these recruitment processes for CD81, a member of the tetraspanin family of proteins that have been implicated previously in cancer progression. We found that genetic deficiency in CD81 reduced tumor growth and metastasis in two genetic mouse backgrounds and multiple tumor models. Mechanistic investigations revealed that CD81 was not required for normal development of Treg and MDSC but was essential for immunosuppressive functions. Notably, adoptive transfer of wild-type Treg into CD81-deficient mice was sufficient to promote tumor growth and metastasis. Our findings suggested that CD81 modulates adaptive and innate immune responses, warranting further investigation of CD81 in immunomodulation in cancer and its progression.
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, California.
Felipe
F
Vences-Catalán
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, California.
Ranjani
R
Rajapaksa
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, California.
Minu K
MK
Srivastava
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, California.
Aurelien
A
Marabelle
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, California.
Chiung-Chi
CC
Kuo
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, California.
Ronald
R
Levy
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, California. slevy@stanford.edu.
Shoshana
S
Levy
D056704:Adaptive Immunity / Q000276:immunology; D019264:Adoptive Transfer; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D007113:Immunity, Innate / Q000276:immunology; D056747:Immunomodulation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D060225:Tetraspanin 28 / Q000235:genetics* / Q000378:metabolism; D019139:Tumor Escape / Q000276:immunology*
C554799:Cd81 protein, mouse; D060225:Tetraspanin 28