Although elevated CD4+Foxp3+ regulatory T cell (Treg) frequencies within tumors are well documented, the functional and phenotypic characteristics of CD4+Foxp3+ and CD4+Foxp3− T cell subsets from matched blood, healthy colon, and colorectal cancer require in-depth investigation. Flow cytometry revealed that the majority of intratumoral CD4+Foxp3+ T cells (Tregs) were Helios+ and expressed higher levels of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and CD39 than Tregs from colon and blood. Moreover, ∼30% of intratumoral CD4+Foxp3− T cells expressed markers associated with regulatory functions, including latency-associated peptide (LAP), lymphocyte activation gene-3 (LAG-3), and CD25. This unique population of cells produced interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), and was ∼50-fold more suppressive than Foxp3+ Tregs. Thus, intratumoral Tregs are diverse, posing multiple obstacles to immunotherapeutic intervention in colorectal malignancies.
Laparoscopic recto-sigmoidectomy postcolonoscopic decompression is a good option for patients with sigmoid volvulus. Surgical complications are minimal and recovery is quick.
Heat shock protein 70 has known functions that promote antitumor immune responses. Its overexpression in colorectal cancers with microsatellite instability may be pivotal to explaining these tumors' enhanced immunogenicity and improved prognosis.
The relationship between the adaptive CD4 þ T-cell response and human cancer is unclear. The oncofetal antigen 5T4 is expressed in many human carcinomas, including colorectal cancer cells, but has limited expression on normal tissues. We previously identified anti-5T4 CD4 þ T cells in a proportion of patients with colorectal cancer, and we extended this study to examine whether the quality or quantity of the T-cell response reflects tumor stage. An overlapping peptide library spanning 5T4 was used as a target to enumerate cognate IFN-g
cells [measured as spot-forming cells (SFC)/10 5 cultured T cells] in peripheral blood-derived lympho-cytes following a 14-day in vitro culture period comparing patients preoperatively (n ¼ 27) to healthy controls (n ¼ 17). Robust 5T4-specific T-cell responses were present in 100% of healthy donors. There was a steady loss of T-cell responses with advancing tumors with a significant negative correlation from stage I to III (P ¼ 0.008). The predictability of the decline meant <200 SFC/10 5 were only found in subjects with stage III colorectal cancer.
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