Use of alpha,25-dihydroxyvitamin D3 treatment to stimulate immune infiltration into head and neck squamous cell carcinoma.
Prior studies have shown that treatment of head and neck squamous cell carcinoma (HNSCC) patients with 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] reduced intratumoral levels of immune inhibitory CD34(+) progenitor cells while increasing levels of mature progeny dendritic cells. This finding was extended to a pilot study to determine whether 1,25(OH)(2)D(3) treatment concurrently increases levels of intratumoral CD4(+) and CD8(+) T cells, increases intratumoral levels of immune cells expressing the early activation marker CD69, and prolongs time to HNSCC recurrence. The clinical trial comprised 16 patients with newly diagnosed HNSCC being untreated and 16 patients being treated with 1,25(OH)(2)D(3) during the 3-week interval between cancer diagnosis and surgical treatment. Immunologic effects of treatment were monitored by immunohistochemical analyses of surgically removed HNSCC. Clinical effectiveness of 1,25(OH)(2)D(3) treatment in this study was measured by the time to HNSCC recurrence. HNSCC tissues of patients who received treatment with 1,25(OH)(2)D(3) contained increased levels of CD4(+) cells and, more significantly, CD8(+) T cells. Also prominent was an increase in cells expressing the lymphoid activation marker CD69. Results of this pilot study suggest that patients treated with 1,25(OH)(2)D(3) had a lengthier time to tumor recurrence compared with patients who were not treated before surgery.
Walsh
Jarrett E
JE
Research Services, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, USA.
Clark
Anna-Maria
AM
Day
Terry A
TA
Gillespie
M Boyd
MB
Young
M Rita I
MR
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002117:Calcitriol / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology* / Q000532:radiotherapy / Q000601:surgery; D002452:Cell Count; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D053208:Kaplan-Meier Estimate; D037181:Lectins, C-Type / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016896:Treatment Outcome; D000099192:CD69 Antigens
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002117:Calcitriol; D037181:Lectins, C-Type; D000099192:CD69 Antigens