Intratumoral T cells, tumor-associated macrophages, and regulatory T cells: association with p53 mutations, circulating tumor DNA and survival in women with ovarian cancer.
OBJECTIVE
Forty percent of women with ovarian cancer have circulating free tumor DNA. We sought to determine if the tumor immune infiltrate varied based on tumor p53 mutation status or presence of circulating tumor DNA.


METHODS
We performed immunohistochemistry on 119 ovarian cancer specimens with CD3 and CD8 (Intratumoral T cells (TILs)), CD68 (tumor-associated macrophages (TAMs)), and FoxP3 (T regulatory cells (Tregs)). Tumors had been previously sequenced for mutations in exons 4-10 of p53, and plasma from women characterized for free tumor DNA.


RESULTS
TIL and TAM levels were positively correlated (P<0.0001). High levels of TILs were identified in 54 of 119 tumors (45.4%). No survival difference was identified according to the presence of TILs or TAMs. Patients with greater TILs were more likely to be optimally cytoreduced (P=0.005). p53 mutations were associated with more TILs (P=0.008). The presence of circulating tumor DNA did not correlate with TILs, TAMs, or Tregs. In the subgroup with a low host antitumor immune response, the intermediate response Tregs group did have a survival advantage (P=0.049).


CONCLUSIONS
p53 mutations are associated with higher levels of TILs. The ratio of Tregs to TILS may be more important than absolute levels. A brisk T cell response within the tumor predicts adequacy of cytoreduction, suggesting successful cytoreduction may be partially due to underlying tumor biology and host response.
Shah
Chirag A
CA
University of Washington Medical Center, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Seattle, Washington 98195, USA. cshah@u.washington.edu
Allison
Kimberly H
KH
Garcia
Rochelle L
RL
Gray
Heidi J
HJ
Goff
Barbara A
BA
Swisher
Elizabeth M
EM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008264:Macrophages / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53