Stromal CD4 (+) T Cell Subsets Mediate Antitumor Cytotoxic Immune Responses in Human Colorectal Carcinoma.

BACKGROUND/AIM: The local immune response in colorectal cancer is closely related to prognosis and therapeutic efficacy. In this study, histological analyses were performed to determine the phenotype of tumor-infiltrating lymphocytes (TILs) and their infiltration in the stromal and intratumoral regions, aiming to elucidate their interactions and prognostic effects. PATIENTS AND METHODS: Multiplex fluorescent labeling was performed using surgically resected colorectal cancer specimens to investigate the infiltration of CD45RO (+) TILs, which exhibit cytotoxicity, and subsets of CD4 (+) TILs, identified by their characteristic transcription factor expression. RESULTS: The degree of CD45RO (+) TIL infiltration in the entire observation field or stromal area was not associated with prognosis. However, a high degree of infiltration in the tumor nest (intratumoral area) was significantly associated with a favorable prognosis. CD4 (+) TILs and their subsets were not associated with prognosis. However, stratified analyses revealed that a high degree of infiltration of stromal CD4 (+) TILs and the subsets T helper (Th)1, Th2, Th17, and regulatory T cells is necessary for the association between high intratumoral CD45RO (+) TIL infiltration and favorable prognosis. CONCLUSION: A sufficient degree of infiltration of stromal CD4 (+) TIL subsets is required for intratumoral CD45RO (+) TILs to exert toxicity against cancer cells. This highlights the significance of stromal immune reactions in achieving effective cytotoxic immune responses in the intratumoral area and demonstrates the critical role of the spatial distribution pattern of TILs in exerting their functions.

CD15+ Bone Marrow-derived Cells Are Regulators of Immune Response in ARG1-producing Colorectal Cancer Cells.

BACKGROUND/AIM: Bone marrow-derived cells regulate the antitumor functions of tumor infiltrating lymphocytes (TILs) through arginase 1 (ARG1)-dependent metabolism. This study examines which ARG1-producing lineage is responsible for the inhibitory function of TILs. MATERIALS AND METHODS: Multiplexed immunohistochemistry was performed for CD11b, CD163, CD68, and CD15, together with ARG1 expression and CD3+ TIL infiltration estimation in human colorectal cancer specimens. RESULTS: Stratified survival analyses demonstrated that a large number of CD3+ TILs is a favorable prognostic factor in subgroups with a high level of ARG1+ infiltration and in the subgroup with a low level of ARG1- CD15+ infiltration. Calculation of the ARG1+/ARG1- ratio demonstrated that CD3+ TIL infiltration was prognostic in the subgroup with a low ARG1+/ARG1- ratio for CD15+ cells, contrary to other lineages. CONCLUSION: Tumor infiltrating CD15+ cells, the majority of which show polymorphonuclear features, are responsible for the ARG1-dependent T-cell dysfunction in human colorectal cancer.

[A Case of Diffuse Large B-Cell Lymphoma of the Testis, Which Also Developed in the Rectum after Resection of a Large B-Cell Lymphoma].

A man aged 65 years had undergone high orchidectomy of the right testis for diffuse large B-cell lymphoma(DLBCL) occurring primarily in the testis 11 months before. Although he was referred to another hospital for postoperative chemotherapy, he refused the treatment by self-judgement. For 1 month, he had been experiencing melena and anal pain, so he visited our department in June. Rectal palpation revealed a sub-circumference tumor palpable from the anal margin, in which a part protruded outside the anus. CT revealed a sub-circumference hypertrophic wall from the rectal Ra to the anus and intramural enlarged lymph nodes, without metastases to the other organs. Systemic gallium scintigraphy detected a strong concentration in the rectum. The endoscopic examination of the inferior region revealed a circumference type 2 tumor at Rb, and biopsy revealed DLBCL. Clinically, this case was considered a testoid DLBCL with rectal metastasis. Therefore, we performed laparoscopic rectal amputation in July, XX. sT3N1b, cM0. The postoperative course was uneventful. After the patient was discharged from our department, he received chemotherapy at another hospital. At present, 4 years 0 month postoperatively, the patient condition is favorable without recurrence. When perforation occurs in gastrointestinal DLBCL, the start of chemotherapy is delayed and the primary lesion worsen. Therefore, we performed surgical therapy first. Such cases must be evaluated for metastases or new lesions carefully.

[A Case of Isolated Metachronous Splenic Metastasis after Rectal Cancer Surgery].

A 50-year-old woman underwent laparotomic anterior resection(D3)and total hysterectomy with bilateral adnexectomy (type 2, 3.0×4.5 cm, pT4a[SE], N1a, M1c2[ovary and peritoneum], H0, P1, PUL0, stage Ⅳc, tub2>por, Cur B)for ovarian metastasis from rectal cancer in June 20XX. During the outpatient visit in May, 2 years and 11 months after surgery, a splenic tumor was found on abdominal contrast-enhanced CT, without distant metastasis in other organs. In July 20XX, laparoscopic splenectomy was performed for suspected splenic metastasis of rectal cancer. The specimen of the resected tumor showed pathological findings consistent with metastasis of rectal cancer. Currently, the patient is being followed up without any sign of recurrence. Herein, we report a rare case of isolated metachronous splenic metastasis, whose associated prognosis might be improved by surgical treatment, in reference to the literature.

[Colorectal Cancer Associated with Crohn's Disease-A Case Report].

We report a case of colorectal cancer associated with Crohn's disease in a 50-year-old man. He had been diagnosed with Crohn's disease 26 years before and had undergone sigmoidectomy for sigmoid colon stenosis 19 years before. Ileal resection, was performed for ileus stenosis 12 years before. Three years before, partial resection of the small intestine was performed for perforation of the small intestine. During this period, the medical treatment was continued, but the patient experienced remission and exacerbation. He complained of anal pain at a regular outpatient visit, and endoscopic examination showed an elevated lesion immediately above the dentate line. Adenocarcinoma Group 5 was detected on biopsy. The diagnosis was rectal cancer(cT2N3M0, StageⅢb). We performed an abdominoperineal resection, a D3 lymph node dissection, and colostomy. Chemotherapy with mFOLFOX6 was provided postoperatively. The patient has survived without recurrence for 1 year and 6 months after the surgery.