Phenotypic plasticity and increased tissue infiltration of TREM1+ mono-macrophages following radiotherapy in rectal cancer. [scRNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA1167200 | ENA |
REPOSITORIES: ENA
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Project description:Our previously reported phase II and phase III trials have demonstrated that short-course radiotherapy (SCRT) combined with neoadjuvant immunochemotherapy (SIC) has led to clinical benefits in locally advanced rectal cancer (LARC). Characterization of the molecular mechanisms underlying responses to SIC may lead to improved treatment strategies. Here, we prospectively collected and applied multi-omic analyses to paired pre- and post-treatment LARC specimens undergoing SIC. The TREM1+ mono-macrophages subsets that display a pro-inflammatory phenotype are identified and correlate with complete response to SIC. Mechanically, ionizing radiation (IR) induces peripheral TREM1+ mono-macrophages expansion in tumors. Following IR, loss of TREM1 in mono-macrophages undermines antitumor immunity by altering mono-macrophages differentiation and inhibiting CD8+ T cell infiltration and activation. The TREM1+ mono-macrophages response may rely on activation of key inflammatory pathways, including NF-κB signaling and Toll-like receptor pathway. Pharmacological inhibition of TREM1 abolishes IR-induced immunoactivation and reduces combined IR and/or anti-PD-1 treatment. Thus, we establish a crucial role of a mono-macrophages state in mediating effective cancer therapy.
2024-11-20 | GSE278406 | GEO
Project description:Our previously reported phase II and phase III trials have demonstrated that short-course radiotherapy (SCRT) combined with neoadjuvant immunochemotherapy (SIC) has led to clinical benefits in locally advanced rectal cancer (LARC). Characterization of the molecular mechanisms underlying responses to SIC may lead to improved treatment strategies. Here, we prospectively collected and applied multi-omic analyses to paired pre- and post-treatment LARC specimens undergoing SIC. The TREM1+ mono-macrophages subsets that display a pro-inflammatory phenotype are identified and correlate with complete response to SIC. Mechanically, ionizing radiation (IR) induces peripheral TREM1+ mono-macrophages expansion in tumors. Following IR, loss of TREM1 in mono-macrophages undermines antitumor immunity by altering mono-macrophages differentiation and inhibiting CD8+ T cell infiltration and activation. The TREM1+ mono-macrophages response may rely on activation of key inflammatory pathways, including NF-κB signaling and Toll-like receptor pathway. Pharmacological inhibition of TREM1 abolishes IR-induced immunoactivation and reduces combined IR and/or anti-PD-1 treatment. Thus, we establish a crucial role of a mono-macrophages state in mediating effective cancer therapy.
2024-11-20 | GSE278405 | GEO
Project description:Phenotypic plasticity and increased tissue infiltration of TREM1+ mono-macrophages following radiotherapy in rectal cancer. [RNA-Seq]
| PRJNA1167199 | ENA
Project description:With a view to developing novel biomarkers of the efficacy of radiotherapy in patients with rectal cancer, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy. Repeat biopsy did not increase toxicity. Radiotherapy induced the expression of genes involved in oxidative stress, signal transduction, apoptosis and immune response.
2011-12-12 | GSE26027 | GEO
Project description:Specific cell types from orthotopic murine rectal tumors were sequenced to explore the effect that short course radiotherapy has on the immune response.
2023-08-07 | GSE227738 | GEO
Project description:With a view to developing novel biomarkers of the efficacy of radiotherapy in patients with rectal cancer, we measured gene expression profiles on biopsies taken before and during preoperative radiotherapy. Repeat biopsy did not increase toxicity. Radiotherapy induced the expression of genes involved in oxidative stress, signal transduction, apoptosis and immune response. Two rectum tumor biospsies for each patient (6 cases) : before RT and one hour after a dose of 7.2 Gy (4th fraction) during RT.
2011-12-12 | E-GEOD-26027 | biostudies-arrayexpress
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:Exosomes may be used as biomarkers for the prediction and monitoring of response to anti-cancer treatment, yet relevant knowledge is very limited in the case of rectal cancer. Here we applied a combined proteomic and metabolomic approach to reveal exosome components connected with different responses to neoadjuvant radiotherapy in this group of patients and processes associated with identified discriminatory molecules. Moreover, the composition of serum-derived exosomes and a whole plasma was analyzed in parallel to compare the biomarker potential of both specimens, which revealed the highest capacity of exosome proteome to discriminate samples of patients with different responses to radiotherapy.
2022-04-04 | PXD031556 | Pride
Project description:Biopsy specimens were collected from rectal cancer before starting preoperative radiotherapy.The expression profiles were determined using Affymetrix Human Genome U95 version 2 arrays.Comparison between the sample groups allow to identify a set of discriminating genes that can be used for characterization of responders and nonresponders to preoperative radiotherapy in rectal cancer. Keywords: repeat
2006-03-29 | GSE3493 | 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 “signature” 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 (χ2=11•793; p= 0•001) and TS expression (χ2=10•589; p= 0•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.
2012-04-25 | GSE29298 | GEO