The aim of this research was to investigate the correlation of immunologic factors in the tumor environment of breast cancer, using immunohistological staining to evaluate the expression of programmed death 1/programmed death ligand 1 (PD‐1/PD‐L1), phosphatase and tensin homolog (PTEN), tumor infiltrating lymphocytes (TILs), and macrophages, and to analyze the association between the immunologic factors and clinical outcome for patients with early stage breast cancer (EBC). A total of 97 EBC patients who underwent standard surgery were investigated. Expression of PD‐1/PD‐L1 and PTEN and the density of CD3+ TILs, CD8+ TILs, and CD163+ macrophages were evaluated by immunohistochemical analysis. The association between the immunologic factors and clinical outcome was statistically analyzed. The density of CD3+ TILs, CD8+ TILs, and CD163+ macrophages and non‐expression of PTEN was significantly higher in cases of triple negative breast cancer. CD8+ TIL density and CD8+/PD‐L1+ expression were predictive factors for disease‐free survival and overall survival (OS). Human epidermal growth factor 2 (HER2)‐positive patients with PTEN expression and luminal/HER2‐negative patients without PD‐L1 expression had significantly longer OS compared to patients without PTEN expression (P = 0.049) and with PD‐L1 expression (P = 0.036), respectively. Furthermore, patients with PD‐L1+/CD8+ expression had worse median progression‐free survival (P = 0.022) and median OS (P = 0.037) compared with patients without PD‐L1+/CD8+ expression. The CD3+ TILs, CD8+ TILs, and CD163+ macrophages were shown to infiltrate the tumor area of EBC. In particular, triple negative breast cancer had a higher rate of TIL infiltration within the tumor environment. Expression of PTEN and lack of PD‐L1 expression were associated with favorable survival in HER2‐positive and luminal/HER2‐negative EBC patients, respectively. The PD‐L1 expression combined with CD8+ density was significantly associated with an aggressive clinical outcome.
A 63-year-old man, who had undergone total gastrectomy and Roux-en-Y reconstruction for gastric cancer 10 years previously, was admitted to our hospital with complaints of abdominal pain, palpable abdominal tumor, and hematemesis. On admission, the abdominal tenderness was improving and no abdominal tumor was palpable. Mild inflammatory changes and anemia were noted on blood examination. Abdominal computed tomography revealed a tumor with a layered structure in the left abdomen. The patient was diagnosed with intestinal obstruction secondary to intussusception, and surgery was performed. Retrograde intussusception was found at the site of the Y anastomosis. We conducted manual reduction using the Hutchinson procedure. The intestinal color after the reduction was good, and no intestinal resection was required. Postoperative recovery was uneventful, and the patient was discharged 12 days after surgery. Reports of jejunal intussusception after total gastrectomy with Roux-en-Y reconstruction are relatively rare. Here, we report a case of jejunal intussusception after total gastrectomy with Roux-en-Y reconstruction.
We undertook an early phase II study of mixed 19‐peptide cancer vaccine monotherapy for 14 advanced metastatic triple‐negative breast cancer (mTNBC) patients refractory to systemic chemotherapy to develop a new type of cancer vaccine. The treatment protocol consisted of a weekly vaccination for 6 weeks, and there were no severe adverse events related to the vaccination throughout the trial. Increase of peptide‐specific IgG against the vaccinated human leukocyte antigen‐matched peptides, but not against the nonmatched peptides, was positively correlated with overall survival (OS) (P < .01). The median OS was 11.5 or 24.4 months in all 14 patients or the 10 patients who completed the vaccination. The patients with lower C‐reactive protein levels or 3 or fewer systemic chemotherapies were favorable candidates for this treatment. Advancement of this therapy to the next stage of study could be warranted based on the safety and immune boosting determined herein (clinical trial registration number: UMIN000014616).
164 Background: Our previous phase II clinical trial has indicated that the therapeutic selected personalized peptide vaccines (PPV) were effective for boosting anticancer immunity and the immune response after PPV was associated with the clinical outcome as a prognostic factor for metastatic breast cancer (mBC). Based on the data from the PPV studies, we have conducted an early phase II study to evaluate the safety and the efficacy of a new regimen using multiple peptide vaccines (KRM-19) for pts with metastatic TNBC. Methods: KRM-19 consisted of 19 mixed peptides which were chosen from the previously reported 31 PPVs according to their anti-tumor immunologic effect and safety profile for mBC pts. All patients had histologically confirmed measurable ER-PgR-Her2- mBC and their human leukocyte antigen (HLA)-A molecules should be each of -A2, A3, A11, A24, A26, A31, or A33. KRM-19 (19mg/ml) was administrated subcutaneously in order with schedule of every week for a total of 6 doses. The concurrent conventional chemo- and/or endocrine therapy was not permitted for the combination, but was available for post-study treatment. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses were conducted before and after vaccination. Levels of IgG reactive to each of the 19 peptides in the pre- and post-vaccination plasma were measured using the LUMINEX system at every 6 vaccinations. Peptide-specific CTL responses were examined by INF-ɤ ELISPOT. Clinical response was evaluated by RECIST criteria. Results: 10 patients with refractory metastatic TNBC received all 6 vaccines and 10/10 patients experienced Grade 1-2 skin reaction at injection site, 5/10 pts had Grade 2-3 liver function disorder, 3/10 and 1/10 pts had Grade 2 bone marrow suppression and nausea, respectively. The clinical responses were assessed in 8 pts included 1 PR case, 4 SD cases, and 3 PD cases. The evaluation of other clinical and immunologic data is underway. Conclusions: Subcutaneous KRM-19 vaccine administration was safe and resulted in a 12.5% objective response and 62.5% clinical benefit rate in TNBC pts, warranting further larger scale study. Clinical trial information: UMIN000014616.
Purpose: Our results from the previous clinical trials using personalized peptide vaccines (PPV) combined conventional chemo-hormonal therapies have confirmed the potential for clinical benefit in patients who had higher IgG antibody and/or CTL response to the immunized PPV (SABCS 2018 U Toh etc.). The aim of this study is to evaluate the association between the serum immunologic factors including cytokines, haptoglobin (HP), B-cell activating factor (BAFF) etc. and the clinical outcome of patients(pt) with metastatic breast cancer (mBC) who treated by personalized peptide vaccines (PPV). Methods: Peripheral blood samples from 57 pts and 52 pts obtained before and after the vaccination of PPV, respectively. Serum HP and IL-6 were analyzed by ELISA(R&D Systems, Life Technologies)and bead-based multiplex assays(Luminex 200 system)were performed for GM-CSF,IFN-γ,TNF-α, BAFF, TGF-β, IFNγ-induced protein 10(IP-10), IL-1β, IL-2,-4,-5,-8, -10. The association between each factor and clinical outcome was statistically evaluated. Results: Pt’s group (n=28) with low BAFF and high HP level (>544 pg/ml), high IFN-γ and high HP level or low IL-8 and high HP level before PPV treatment showed a significantly shorter median survival time (MST; p=0.015;0.068;0.002, respectively). There was no difference in high BAFF, low IFN-γ or high IL-8 level group(n=29). In contrast, pt’s group with low serum level of IL-10, GM-CSF, IL-5, IL-4 and low HP level (<544 pg/ml MV) after PPV treatment associated with significantly shorter MST (p=0.002; 0.001; 0.001; <0.001, respectively). Conclusions: The combination of serum levels of HP and BAFF, IFN-γ or cytokines of IL-8, -10, - 5, -4 might be useful prognostic biomarkers for mBC pts receiving PPV therapy. Citation Format: Uhi Toh, Shuko Saku, Yuko Takao, Sayaka Sakurai, Miki Takenaka, Shigeki Shichijo, Kyogo Itoh, Yoshito Akagi. Analysis of serum immune biomarkers for response to therapeutic personalized peptide vaccination in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-21.
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