TY - JOUR
T1 - IL4 from T follicular helper cells downregulates antitumor immunity
AU - Shirota, Hidekazu
AU - Klinman, Dennis M.
AU - Ito, Shuku Ei
AU - Ito, Hiroyasu
AU - Kubo, Masato
AU - Ishioka, Chikashi
N1 - Publisher Copyright:
© 2017 AACR.
PY - 2017/1
Y1 - 2017/1
N2 - Immune cells constitute a large fraction of the tumor microenvironment and modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL4 in particular is upregulated. Here, we demonstrate that T follicular helper (Tfh) cells arise in tumor-draining lymph nodes where they produce an abundance of IL4. Deletion of IL4-expressing Tfh cells improves antitumor immunity, delays tumor growth, and reduces the generation of immunosuppressive myeloid cells in the lymph nodes. These findings suggest that IL4 from Tfh cells affects antitumor immunity and constitutes an attractive therapeutic target to reduce immunosuppression in the tumor microenvironment, and thus enhance the efficacy of cancer immunotherapy.
AB - Immune cells constitute a large fraction of the tumor microenvironment and modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL4 in particular is upregulated. Here, we demonstrate that T follicular helper (Tfh) cells arise in tumor-draining lymph nodes where they produce an abundance of IL4. Deletion of IL4-expressing Tfh cells improves antitumor immunity, delays tumor growth, and reduces the generation of immunosuppressive myeloid cells in the lymph nodes. These findings suggest that IL4 from Tfh cells affects antitumor immunity and constitutes an attractive therapeutic target to reduce immunosuppression in the tumor microenvironment, and thus enhance the efficacy of cancer immunotherapy.
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U2 - 10.1158/2326-6066.CIR-16-0113
DO - 10.1158/2326-6066.CIR-16-0113
M3 - Article
C2 - 27920023
AN - SCOPUS:85016120063
SN - 2326-6066
VL - 5
SP - 61
EP - 71
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 1
ER -