Immune Microenvironment: New Insight for Familial Adenomatous Polyposis

Yang, Jun; Zhou, Wen; Li, Wenliang; Sun, Xiaotian; Ma, Junrui; She, Xueke; Zhang, Hongbin; Tu, Changling; Wang, Guoqiang; Huang, Depei; Shen, Xudong; Dong, Jian; Zhang, Hushan

doi:10.3389/fonc.2021.570241

Cited by 8 publications

(11 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another modality that has brought great interest is chemoprevention in patients with FAP, which consists of using drugs to reduce the burden of polyps and delay the time of surgical intervention [ 9 ]. An ideal chemopreventive agent would be one that has a mechanism of action related to the pathogenesis of the disease and is safe and easily tolerated over a prolonged treatment period to produce a significant clinical effect [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…The most widely used COX-inhibiting drugs have been sulindac, celecoxib, rofecoxib, fish oil, and aspirin. Multiple studies have shown that these drugs, alone or with a second one, such as difluoromethylornithine (DFMO) or erlotinib, are still ineffective [ 9 - 11 ]. Another signaling pathway of interest has been the mammalian target of rapamycin (mTOR), which is involved in angiogenesis, uncontrolled cellular anabolism, and metastatic transformation [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Familial Adenomatous Polyposis: Case Report and Literature Review

Chaves¹,

Chaves-Cabezas²,

Parra‐Medina³

et al. 2022

Cureus

View full text Add to dashboard Cite

Familial adenomatous polyposis (FAP) is an autosomal inheritance disease characterized by 100 or more adenomatous polyps in the colon and rectum with a high risk of developing colorectal carcinoma (CRC). The management of this disease is based on early screening and timely follow up, with subsequent planning of risk-reducing or therapeutic surgeries. We present a case of a patient with a strong family history of FAP with a "de novo" diagnosis of CRC. Furthermore, a literature discussion of current and future perspectives of treatment is performed.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Familial Adenomatous Polyposis: Case Report and Literature Review

Chaves¹,

Chaves-Cabezas²,

Parra‐Medina³

et al. 2022

Cureus

View full text Add to dashboard Cite

show abstract

“…Endoscopic removal of polyps can effectively prevent the occurrence of bowel cancer, thus delaying the time of surgery, preserving the normal physiological function of the intestine, and thus improving the quality of life of patients. [ 4 , 7 ] The patient was a young woman who was unwilling to undergo surgical treatment, so endoscopic treatment was selected, which was in line with the current clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…Repeated resection of colorectal polyps can ensure the quality of life of FAP patients and delay the disease progression to a certain extent. [ 4 , 7 ] When a patient’s polyp becomes cancerous, surgical treatment is generally recommended. What happens if the patient doesn’t have surgery?…”

Section: Introductionmentioning

confidence: 99%

Metformin combined with endoscopic therapy in patients with familial polyposis associated with carcinoma: A case report

Sun

et al. 2022

Medicine

View full text Add to dashboard Cite

Rationale: Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disease, with a very high cancer rate. At present, endoscopic resection of polyps ≥ 1 cm is often chosen for patients with non-cancerous polyps who are unwilling to undergo surgery, and regular review is conducted. Once the polyps are pathologically confirmed to be cancerous, surgical resection of the diseased large intestine is generally recommended, but surgery often leads to a series of complications. So what do you do with cancer patients who don’t want surgery? Patient concerns: A 19-year-old woman presented with intermittent hematochezia with abdominal pain. A colonoscopy revealed hundreds of intestinal polyps. Diagnoses: The patient had a family history of FAP, and there were hundreds of polyps in the intestine. The pathology was adenomatous, and some polyps became cancerous, which met the diagnostic criteria of FAP. Interventions: Endoscopic examination was arranged for the patient, the resection of intestinal polyps ≥ 1 cm was given priority, and other polyps were removed as far as possible. After that, metformin 500 mg orally was given twice a day, and endoscopic follow-up was conducted every 6 months. During each endoscopic follow-up, intestinal polyps ≥ 1 cm were preferred to be removed, and other polyps were removed as far as possible. Outcomes: The patient’s abdominal pain and blood in the stool disappeared after endoscopic treatment. Cancerous polyps were found at the second and third follow-up visits, but the patient always refused surgical treatment. After 4 years of follow-up, polyp load was significantly reduced, abdominal pain and bloody stool symptoms did not appear again, and imaging examination showed no tumor recurrence and metastasis. Lessons: Endoscopic polyp resection is an important method to treat the clinical symptoms of FAP. Metformin combined with endoscopic therapy is a good alternative for patients with familial polyposis who do not want surgery. When the polyp is cancerous and the polyp is radically resected by the endoscope, if the patient refuses additional surgery, oral metformin combined with endoscopic follow-up can be considered.

show abstract

“…Some studies have demonstrated a lower expression of Th1 cytokines, a shift to a Th2 cytokine profile [ 4 , 15 ], and a decrease in cytotoxic CD8+ T cell counts along ACS [ 17 , 18 ], whereas others have suggested an increase in the density of T lymphocytes, regulatory T cells, and macrophages during tumor progression [ 4 , 14 , 16 ]. Likewise, little information is available regarding the comparison of human colorectal neoplastic lesions arising from a sporadic or hereditary background, since most studies on hereditary cancer have used mouse models, especially APCmin mice [ 19 ]. Furthermore, most of the studies in human colorectal cancer focused on MSI tumors.…”

Section: Introductionmentioning

confidence: 99%

The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence

Freitas

Gullo

Garcia

et al. 2021

IJMS

View full text Add to dashboard Cite

Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma–carcinoma sequence (ACS). Methods. We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). Results. The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. Conclusions. The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.

show abstract

Immune Microenvironment: New Insight for Familial Adenomatous Polyposis

Cited by 8 publications

References 107 publications

Familial Adenomatous Polyposis: Case Report and Literature Review

Familial Adenomatous Polyposis: Case Report and Literature Review

Metformin combined with endoscopic therapy in patients with familial polyposis associated with carcinoma: A case report

The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence

Contact Info

Product

Resources

About