Immune impact of neoadjuvant chemo/radio-therapy in the pancreatic cancer microenvironment
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PROVIDER: PRJNA531483 | ENA |
REPOSITORIES: ENA
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Project description:Pancreatic ductal adenocarcinoma (PDAC) has dismal five-year survival (<9%). We examined the impact of neoadjuvant FOLFIRINOX alone or in combination with radiation therapy (conventional radiotherapy, XRT, or stereotactic body radiotherapy, SBRT) on immunologically relevant genes in the PDAC tumor microenvironment (TME). We hypothesize conventional therapies may induce immune alterations in the TME that can be leveraged to enhance the efficacy of immunotherapy in PDAC. PDAC patients who underwent upfront surgical resection or who received neoadjuvant FOLFIRINOX with or without neoadjuvant radiotherapy followed by surgical resection were selected for study. The expression of 730 immunologically relevant transcripts was quantitated using the Nanostring PanCancer immune profiling panel (Platform GPL19965). This analysis identified189 genes that were differentially expressed at the RNA level on the basis of neoadjuvant therapy. On average specimens were obtained 6.6-17.0 weeks after the conclusion of neoadjuvant therapy, depending on treatment group. These data provide insight into the immunological effects of standard of care neoadjuvant therapy for resectable/borderline-resectable PDAC. This work provides data to guide strategic new combination therapies for pancreatic cancer.
2019-04-09 | GSE129492 | GEO
Project description:Shotgun Proteomics, Proteomic characterization of the residual PDAC tumor mass after neoadjuvant chemo or combined chemo-radiation therapy
| EGAD00010002388 | EGA
Project description:Background:The international standard of care for the treatment of high-risk breast cancer (BC) consists of neoadjuvant chemotherapy (NACT) and surgery followed by adjuvant whole breast/chest wall irradiation. In this setting, the time interval from the start of NACT to the end of radiotherapy (RT) is usually postponed to 6 months or longer. In addition to this, a high percentage of capsular fibrosis may occur when breast implants are irradiated. Most of these disadvantages could be avoided by using preoperative RT (PRT). PRT is already the standard of care in several other tumor entities (rectal cancer, esophagus carcinoma, lung cancer, and soft tissue sarcoma). Nevertheless, PRT in BC has been tested in several trials, but randomized prospective trials using modern radiation technology and systemic therapies are lacking. The available evidence summarized in this review indicates that PRT may improve survival and reduce long-term toxicity in patients with a higher risk of recurrence and should be consequently tested in a randomized trial. Summary:Prospective, randomized trials concerning PRT in high-risk BC are needed. We plan to conduct a NeoRad trial (NACT followed by PRT in high-risk BC). Key Messages:Prospective, randomized studies concerning PRT in high-risk BC are needed.
| S-EPMC7204855 | biostudies-literature
Project description:Expression profiling of nasopharyngeal carcinoma patients comparing radio-sensitive samples with radio-resistant samples. Two condition-experiments, radio-sensitive and radio-resistant nasopharyngeal carcinoma patients. Biological replicates: 8 radio-sensitive, 12 radio-resistant, different donors in the same hospital. One patient per array.
2013-09-21 | E-GEOD-32389 | biostudies-arrayexpress
Project description:We performed data independent acquisition (DIA)-based proteomics to characterize the proteomes of 67 PDAC resection specimens. Patients received either neoadjuvant chemotherapy or neoadjuvant combined chemo-radiation therapy. We employed DIA, yielding a proteome coverage in excess of 3,500 proteins. The two neoadjuvant therapies yielded highly distinguishable proteome profiles of the residual tumor mass.
| EGAS00001006739 | EGA
Project description:The tumor microenvironment in brain metastases is characterized by high myeloid cell content with immune-suppressive and cancer-permissive functions. Moreover, brain metastases induce the recruitment of lymphocytes. Despite their presence, T cell-directed therapies fail to elicit effective anti-tumor immune responses. Here we seek to evaluate the applicability of radio-immunotherapy to modulate tumor immunity and overcome inhibitory effects that diminish anti-cancer activity. Radiotherapy-induced immune modulation resulted in an increase in cytotoxic T cell numbers and prevented the induction of lymphocyte-mediated immune suppression. Radio-immunotherapy led to significantly improved tumor control with prolonged median survival in experimental breast-to-brain metastases. However, long-term efficacy was not observed. Recurrent brain metastases showed accumulation of blood-borne PD-L1+ myeloid cells after radio-immunotherapy indicating the establishment of an immune-suppressive environment to counteract re-activated T cell responses. This finding was further supported by transcriptional analyses indicating a crucial role for monocyte-derived macrophages in mediating immune-suppression and regulating T cell function. Therefore, selective targeting of immune suppressive functions of myeloid cells is expected to be critical for improved therapeutic efficacy of radio-immunotherapy in brain metastases.
2021-02-12 | GSE164049 | GEO
Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.
2012-04-24 | E-GEOD-29298 | biostudies-arrayexpress
Project description:Expression profiling of nasopharyngeal carcinoma patients comparing radio-sensitive samples with radio-resistant samples.
2013-09-21 | GSE32389 | GEO
Project description:We characterized n=134 HNSCC by Quantseq 3´-RNA-sequencing for their transcriptional profiles in order to analyze differential expression of clinically relevant subgroups, define transcriptionally defined molecular subgroups and to characterize the tumor microenvironment by gene expression devonvolution approaches.
2024-05-16 | GSE235223 | GEO
Project description:Men with clinically localized prostate cancer were treated with 0 to 9 months of neoadjuvant hormone suppression prior to prostatectomy. Keywords: microarray, hormone, 9 men with prostate cancer were assigned to neoadjuvant hormone suppression therapy for 3-6, 6, or 0 months.
2008-12-01 | E-GEOD-9983 | biostudies-arrayexpress