Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

Purpose Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. Methods We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. Results TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. Conclusions Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings (AU)

Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes.

PURPOSE: Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. METHODS: We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. RESULTS: TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. CONCLUSIONS: Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings.

Epithelioid trophoblastic tumor metastatic to the vagina: an immunohistochemical and ultrastructural study.

We describe an epithelioid trophoblastic tumor (ETT) metastatic to the vagina in a 30-year-old Japanese woman. A polypoid tumor in the vaginal orifice was composed of nests of intermediate trophoblastic cells that showed a striking epithelioid appearance. In the hysterectomy specimen, a tumor infiltrated through the myometrium and showed histologic findings similar to those of the vaginal tumor. The tumor cells were positive for cytokeratin, inhibin-alpha, and melanoma cell adhesion molecule (Mel-CAM, CD146) but were only focally positive for human placental lactogen. Electron microscopic examination revealed bundles of well-developed, intermediate-type filaments surrounding the nuclei.

[A case of advanced gastric cancer surviving 3 years and 6 months after resection of Krukenberg's tumor].

Total gastrectomy was performed in a patient with an advanced gastric cancer (stage III). One year and eleven months postoperatively, Krukenberg's tumor was recognized and the prognosis was considered to be poor. A recurrence of ascites was identified. After resection of tumor, CDDP was administered intraperitoneally, and 5-FU tablets were administered orally as a maintenance therapy for a long term. The patient has continued to be in a good condition without any sign of recurrence for three years and six months (ie, five years and five months after previous gastrectomy).

[Percutaneous injection of cisplatin lipiodol suspension (CLS) in rabbit lung, aiming at intratumoral injection therapy for lung cancer].

Cisplatin lipiodol suspension (CLS: cisplatin 20 mg/ml) was percutaneously injected (cisplatin dose, 2, 4 or 6 mg/kg) in normal lungs of 10 rabbits (1.9-2.3 kg) to assess the safety and feasibility of intratumoral injection of CLS for lung cancer. Histological study revealed acute and chronic infiltrates with bronchiolitis and immature fibrosis at the injected lung tissue even at four weeks after injection. Intrathoracic leaks of CLS produced mild and focal fibrinous pleuritis. Intrabronchial leaks of CLS produced peripheral bronchiolitis with regenerative epithelia. However, no noxious parenchymal damage in the lung and surrounding tissues was noted. Neither oil embolism in brain nor renal toxicity was demonstrated. Seven of eight rabbits showed an increase in body weight. Concentration levels of plasma platinum were lower when compared with intravenous injection of cisplatin in the rabbit: highest at 30 minutes and unmeasurable one week after injection. Lipiodol accumulation in mediastinal lymph nodes was demonstrated in two of nine rabbits by X-ray examination, suggesting intralymphatic drainage of CLS. Intratumoral injection of CLS is safe even with CLS leaks in surrounding normal lung tissues and may be a potent therapy for controlling mediastinal lymph nodes metastasized from lung cancer as well as the primary tumor.

[Anticancer effect and side effect of arterial chemoembolization using cis-diamine-dichloroplatinum (II)/4-0-tetrahydropyranyl-adriamycin-lipiodol (CTL) suspension on hepatocellular carcinoma].

Seventeen patients with hepatocellular carcinoma were treated by intraarterial injection of CTL suspension. The doses of CTL suspension, CDDP and THP(mean +/- SD)/injection were 4.1 +/- 1.6 ml, 81.9 +/- 31.6 mg and 13.5 +/- 5.2 mg, respectively. The therapy was given once in 10 patients, twice in 6 and 4 times in one. Over 50 per cent reduction in tumor size was obtained in 5 patients (30%). Fifty or more % decrease in serum alpha-feto-protein (AFP) levels was observed in 3 of 7 patients (43%) with the initial serum AFP level of more than 200 ng/ml, Fever, abdominal pain, nausea and vomiting were noted in most cases. However, they disappeared within 2 weeks after therapy was completed. No severe complications were encountered except one case of a liver abscess which healed by administration of antibiotics. No severe changes in laboratory data were observed. This study suggests that a new method of intraarterial injection must be developed to enhance the therapeutic effect even more, in addition to an increased injection dose of CDDP/THP-LPD and higher concentration of CDDP and THP in LPD.

Recovery curves of the blink reflex during wakefulness and sleep.

The paired shock technique was used to study the effect of sleep on the excitability of the short latency R1 and long latency R2 components of the electrically elicited blink reflex. During wakefulness, R1 returned, after transient potentiation, to its original level in about 150 ms following the conditioning stimulus. Contrastingly, R2 remained profoundly suppressed up to 800 ms, suggesting sustained reduction of excitability of the polysynpatic reflex pathways after the passage of a preceeding impulse. During non-REM and REM sleep, the recovery curve of R1 was similar in character, although different in time course to the one obtained during wakefulness. However, R2 was potentiated rather than suppressed by the conditioning stimulus during both phases of sleep. These findings indicate that, during sleep, the polysynpatic reflex pathways are not inhibited by a preceeding impulse to the same degree as in wakefulness.