The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence

Freitas, João Augusto Teixeira de; Gullo, Irene; Garcia, Diogo; Miranda, Sara; Spaans, Louisa N; Pinho, Lidia Maria de Menezes; Reis, Joana; Sousa, Filipa; Baptista, Manuela; Resende, Carlos; Leitão, Dina; Durães, Cecília; Costa, José Luís; Carneiro, Fátima; Machado, José Carlos

doi:10.3390/ijms22189791

Cited by 4 publications

(4 citation statements)

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“…Involvement of lymphoid cells in CRC stroma, however, is not in general agreement in the research frontier. Using flow cytometry for a comprehensive analysis of immune cells in tumor tissues from a cohort of 69 CRC patients, Li et al claimed that no significant difference was found for the CD4+ and CD8+ T cells between tumor and normal tissues (46), while Freitas et al examined the immune context of sporadic and familial adenomatous polyposis lesions along the colorectal adenomacarcinoma sequence and observed an overall decrease in tumorinfiltrating immune cells along the colorectal tumors (23). During CRC development, immunoediting leads to the generation of plentiful neoantigens presented by both MHC-I and MHC-II that basically require synergetic effects of CD4+ and CD8+ T cells.…”

Section: Discussionmentioning

confidence: 99%

“…Very recently, Wang et al took a digital spatial profiler, a high-plex spatial proteogenomic technology, to analyze 40 antibodies with DNA oligomer conjugation and a panel of probes for 84 mRNAs related with epithelial and immune cells, and concluded that these specific biomarkers were differentially expressed between the tumor and stromal regions at either the transcriptional or translational levels (22). Freitas et al analyzed the immune landscape of the colorectal adenomatous polyps using IHC and found that compared with low-grade dysplasia, high-grade dysplasia was characterized with decreased immune infiltration, increased MHC-I expression, and lower PD-L1 expression (23). With respect to profiling proteomics, LCM was a common means to isolate the tumor and adjacent stroma tissues, followed by proteomic analysis to identify the differentially expressed proteins (DEPs) between the tumor and adjacent stroma.…”

Section: Introductionmentioning

confidence: 99%

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The Comparable Microenvironment Shared by Colorectal Adenoma and Carcinoma: An Evidence of Stromal Proteomics

et al. 2022

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Tumor microenvironment (TME) is a key factor involved in cancer development and metastasis. In the TME of colorectal cancer (CRC), the gene expression status of stromal tissues could influence the CRC process from normal to adenoma then carcinoma; however, the expression status at the protein level has not yet been well evaluated. A total of 22 CRC patients were recruited for this study, and the tissue regions corresponding with adjacent, adenoma, and carcinoma were carefully excised by laser capture microdissection (LCM), including a patient with adenoma and carcinoma. The individual proteomes of this cohort were implemented by high-resolution mass spectrometer under data-independent acquisition (DIA) mode. A series of informatic analysis was employed to statistically seek the proteomic characteristics related with the stroma at different stages of CRC. The identified proteins in the colorectal stromal tissues were much less than and almost overlapped with that in the corresponding epithelial tissues; however, the patterns of protein abundance in the stroma were very distinct from those in the epithelium. Although qualitative and quantitative analysis delineated the epithelial proteins specifically typified in the adjacent, adenoma, and carcinoma, the informatics in the stroma led to another deduction that such proteomes were only divided into two patterns, adjacent- and adenoma/carcinoma-dependent. The comparable proteomes of colorectal adenoma and carcinoma were further confirmed by the bulk preparation- or individual LCM-proteomics. The biochemical features of the tumor stromal proteomes were characterized as enrichment of CD4+ and CD8+ T cells, upregulated pathways of antigen presentation, and enhancement of immune signal interactions. Finally, the features of lymphoid lineages in tumor stroma were verified by tissue microarray (TMA). Based on the proteomic evidence, a hypothesis was raised that in the colorectal tissue, the TME of adenoma and carcinoma were comparable, whereas the key elements driving an epithelium from benign to malignant were likely decided by the changes of genomic mutations or/and expression within it.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Comparable Microenvironment Shared by Colorectal Adenoma and Carcinoma: An Evidence of Stromal Proteomics

et al. 2022

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“… 1 , 2 The etiopathogenesis of most CRCs follows a sequence of events that have been described as the adenoma-carcinoma sequence. 3 , 4 This sequence typically takes more than 10 years to complete in sporadic cancers and can be effectively disrupted via screening. 5 Colonoscopy is considered the most efficacious screening method for reducing CRC incidence and mortality because it allows for the early detection and removal of precancerous polyps and the detection of early-stage CRC.…”

Section: Introductionmentioning

confidence: 99%

Adenoma Detection Rate in Average-Risk Population: An Observational Consecutive Retrospective Study

Zhang

et al. 2023

Cancer Control

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Background Although colonoscopy is considered the most effective tool for reducing colorectal cancer-related morbidity, the age at which average-risk individuals begin colonoscopic screening is undetermined. This study aimed to compare the adenoma and advanced adenoma detection rates according to age and sex in a large average-risk population in the rural areas of Eastern China. Methods This observational, single-center, retrospective study included patients with average colorectal cancer risk and examined the adenoma and advanced adenoma detection rates using age intervals of 5 years. We also compared the size and age of patients with and without advanced adenoma. Results We included 18 928 patients with a median age of 54 years (range 15–90 years), including 10 143 men and 8785 women. The adenoma and advanced adenoma detection rates were 17.08% and 5.24%, respectively, and increased with age in the whole population. The adenoma detection rates increased from 8.97% (aged 40–44) to 14.98% (aged 45–49) and 6.24% (aged 45–49) to 11.00% (aged 50–54) in men and women (both P < .001), respectively. The advanced adenoma detection rates increased from 2.19% (aged 40–44) to 4.76% (aged 45–49) and 1.89% (aged 45–49) to 3.13% (aged 50–54) in men ( P = .002) and women ( P = .056), respectively. Patients with advanced adenomas were significantly older than those with non-advanced adenomas ( P < .001). The tumors in the advanced adenoma group were significantly larger than those in the non-advanced adenoma group ( P < .001). Conclusion The adenoma and advanced adenoma detection rates increased significantly in average-risk population aged 45 years and older, especially in men.

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“…Although a patient's microbiome consists of bacterial, viral, fungal, and archaeal species from a variety of sites throughout the body, tumoral microbes have recently been associated with both the development of CRC as well as the differential responses to cytotoxic therapies, perhaps in association with their ability to regulate immune infiltrates within tumors [8][9][10][11] and modify chemotherapeutic drugs. For example, Escherichia coli isolates from CRC patients were shown to modify 5-fluoroacyl diminishing toxicity to CRC epithelial cells.…”

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confidence: 99%

Young-onset Rectal Cancer

White,

Damania,

Alshenaifi

et al. 2023

Annals of Surgery

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Objective: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers for profiles potentially correlative with disease etiology and biology. Summary Background Data: Young-onset rectal cancer is rapidly increasingly, with one in four new rectal cancer cases occurring under age 50. Its etiology is unknown. Methods: Young-onset (YO-; <50 y old) or later-onset rectal cancer (LORC, ≥50 years old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal tissue (TAN). After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors vs. TANs and YO- vs. LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) vs. non-MPR. Results: Our 107 tumor and 75 TANs from 37 (35%) YO- and 70 (65%) LORCs recapitulated bacterial species previously associated with colorectal cancers (all P<0.0001). YO and LORC tumoral microbiome signatures were distinct. After NT, 13 (12.4%) patients achieved complete pathologic response, while MPR, in 47(44%). Among YORCs, MPR was associated with Fusobacterium nucleaum, Bacteroides dorei, and Ruminococcus Bromii (all P<0.001), but MPR in LORC was associated with Ruminococcus Bromii (P<0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors. Conclusions: Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge furture studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments.

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The Adaptive Immune Landscape of the Colorectal Adenoma–Carcinoma Sequence

Cited by 4 publications

References 34 publications

The Comparable Microenvironment Shared by Colorectal Adenoma and Carcinoma: An Evidence of Stromal Proteomics

The Comparable Microenvironment Shared by Colorectal Adenoma and Carcinoma: An Evidence of Stromal Proteomics

Adenoma Detection Rate in Average-Risk Population: An Observational Consecutive Retrospective Study

Young-onset Rectal Cancer

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