Co-expression of nuclear and cytoplasmic HMGB1 is inversely associated with infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer.
BACKGROUND
The intratumoral infiltration of T cells, especially memory T cells, is associated with a favorable prognosis in early colorectal cancers. However, the mechanism underlying this process remains elusive. This study examined whether high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecule, is involved in the infiltration of T cells and disease progression in locally advanced colon cancer.


METHODS
Seventy-two cases of pathologically-confirmed specimens were obtained from patients with stage IIIB (T3N1M0) colon cancer who underwent radical resection between January 1999 and May 2002 at the Cancer Center of Sun Yat-Sen University. The density of tumor-infiltrating lymphocytes (TILs) within the tumor tissue and the expression of HMGB1 in the cancer cells were examined via immunohistochemical analysis. The phenotype of CD45RO+ cells was confirmed using a flow cytometric assay. The association between HMGB1 expression, the density of TILs, and the 5-year survival rate were analyzed.


RESULTS
The density of CD45RO+ T cells within the tumor was independently prognostic, although a higher density of CD3+ T cells was also associated with a favorable prognosis. More importantly, the expression of HMGB1 was observed in both the nucleus and the cytoplasm (co-expression pattern) in a subset of colon cancer tissues, whereas nuclear-only expression of HMGB1 (nuclear expression pattern) existed in most of the cancer tissues and normal mucosa. The co-expression pattern of HMGB1 in colon cancer cells was inversely associated with the infiltration of both CD3+ and CD45RO+ T cells and 5-year survival rates.


CONCLUSIONS
This study revealed that the co-expression of HMGB1 is inversely associated with the infiltration of CD45RO+ T cells and prognosis in patients with stage IIIB colon cancer, indicating that the distribution patterns of HMGB1 might contribute to the progression of colon cancer via modulation of the local immune response.
Peng
Rui-Qing
RQ
State Key Laboratory of Oncology in South China, 651 Dongfeng R E, 510060 Guangzhou, China.
Wu
Xiao-Jun
XJ
Ding
Ya
Y
Li
Chun-Yan
CY
Yu
Xing-Juan
XJ
Zhang
Xing
X
Pan
Zhi-Zhong
ZZ
Wan
De-Sen
DS
Zheng
Li-Ming
LM
Zeng
Yi-Xin
YX
Zhang
Xiao-Shi
XS
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003600:Cytosol / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis
D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; D017493:Leukocyte Common Antigens