CD8+ and FOXP3+ Tumor-Infiltrating T Cells Before and After Chemoradiotherapy for Rectal Cancer

Shinto, Eiji; Hase, Kazuo; Hashiguchi, Yojiro; Sekizawa, Akinori; Ueno, Hideki; Shikina, Atsushi; Kajiwara, Yoshiki; Kobayashi, Hirotoshi; Ishiguro, Megumi; Yamamoto, Junji

doi:10.1245/s10434-014-3584-y

Cited by 122 publications

(126 citation statements)

References 26 publications

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“…2). The majority support a positive impact on prognosis associated with extensive memory T-cell infiltration in the same cancers we discussed earlier, eg, CRC (Anitei et al, 2014;Boissi ere-Michot et al, 2014;Correale et al, 2012;Kim, Bae, et al, 2015;Ling et al, 2014;Ong et al, 2015;Shinto et al, 2014), bladder (Ingels et al, 2014), breast de Kruijf et al, 2013;García-Martínez et al, 2014;Kim et al, 2013;Mohammed et al, 2013;Park et al, 2012;Rathore et al, 2014;Seo et al, 2013;West et al, 2013), Merkel cell carcinoma (Paulson et al, 2014), glioma (Han et al, 2014), pancreatic (Ino et al, 2013;Tang et al, 2014), head and neck (Balermpas et al, 2014;Czystowska et al, 2013;Millrud et al, 2012;Wallis et al, 2015), cervical (Origoni et al, 2013), NSCLC Hald et al, 2013), gastric Feichtenbeiner et al, 2014;Kim et al, 2014), ovarian (Bachmayr-Heyda et al, 2013;Nielsen et al, 2012;Preston et al, 2013), and HCC (Cariani et al, 2012;Chen et al, 2012;Guo et al, 2007;Huang et al, 2012) (Table 1 and Fig. 2).…”

Section: Role Of T Cellssupporting

confidence: 65%

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

Becht¹,

Giraldo²,

Germain³

et al. 2016

Advances in Immunology

181

136

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Section: Role Of T Cellssupporting

confidence: 65%

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

Becht¹,

Giraldo²,

Germain³

et al. 2016

Advances in Immunology

181

136

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“…In rectal cancer, neoadjuvant radiotherapy may induce inflammation and immune cell infiltration. 41 We exclude a major impact here from since we could verify direct surgery without prior radiotherapy in 42 cases and use of neoadjuvant radiotherapy in only one case.…”

Section: Methodsmentioning

confidence: 99%

Immunoprofiles of colorectal cancer from Lynch syndrome

et al. 2018

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Colorectal cancers associated with Lynch syndrome are characterized by defective mismatch repair, microsatellite instability, high mutation rates, and a highly immunogenic environment. These features define a subset of cancer with a favorable prognosis and high likelihood to respond to treatment with anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) drugs. With the aim to define immune-evasive mechanisms and a potential impact hereof in colorectal cancers from Lynch syndrome versus hereditary cases with retained mismatch repair function, we immunohistochemically and transcriptionally profiled 270 tumors. Lynch syndrome-associated tumors showed an overrepresentation of tumor-infiltrating CD3, CD8 and CD68 positive cells, loss of beta-2-microglobulin (B2M) and up-regulation of PD-L1 on tumor cells. The gene expression signature of Lynch syndrome tumors was characterized by upregulation of genes related to antigen processing and presentation, apoptosis, natural killer cell-mediated cytotoxicity, and T cell activation. Tumors with loss of B2M and up-regulation of PD-L1 showed distinctive immunogenic profiles. In summary, our data demonstrate a complex tumor-host interplay where B2M loss and PD-L1 up-regulation influence immunological pathways and clinical outcome in Lynch syndrome tumors. Immunological classification may thus aid in the preselection of colorectal cancers relevant for treatment with anti-PD-1/PD-L1 therapies.

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“…Scoring of intraepithelial lymphocytes (IELs) and stromal lymphocytes (STLs) was performed as previously reported [17]. CD8 + and FoxP3 + IELs were counted in the densest field using a ×40 objective lens.…”

Section: Immunohistochemistry For Til Scoringmentioning

confidence: 99%

“…Further, to elucidate whether keloid-like collagen and myxoid stroma observed in the resected surgical specimens belong to the original characteristics of the tumor or are newly formed features under the influence of CRT, we compared DR categories in the resected surgical specimens with histological features in pretreatment biopsy specimens. Given that DR categories are related to the density of tumor-infiltrating lymphocytes (TIL) [13,14], we investigated the density of CD8 + T cells and FoxP3 + T cells, a combination of representative populations of cytotoxic and regulatory T cells which reportedly characterize local antitumor immunity in various malignancies receiving neoadjuvant therapy [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

In rectal cancer, the type of desmoplastic response after preoperative chemoradiotherapy is associated with prognosis

et al. 2015

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Although the essential contribution of the desmoplastic reaction (DR) to aggressive tumor behavior is increasingly recognized, its prognostic value has not been investigated in rectal cancer after preoperative chemoradiotherapy. We retrospectively analyzed 101 consecutive patients with rectal cancer treated with short-course chemoradiotherapy followed by surgery (2001-2007). The DR in the resected primary tumor was pathologically classified into three patterns on the basis of products of cancer-associated fibroblasts (CAFs): mature (multilayered fibrotic), intermediate (keloid-like hyalinized), and immature (mostly myxoid). We classified 46 tumors as mature, 30 as intermediate, and 25 as immature DR. In addition, immunostaining of CD8(+) and FoxP3(+) cells was performed to characterize the immune response accompanying DR. Mature DR correlated with higher density of CD8(+) and FoxP3(+) cells in both resected surgical and pretreatment biopsy specimens. A significant association with DR category was observed for T stage, lymphatic invasion, and venous invasion (P ≤ 0.0001-0.0006). Mature DR was significantly associated with higher grade of pathological response (P = 0.0350). The 5-year disease-free survival (DFS) rates were 82, 72, and 47 % for mature, intermediate, and immature DR, respectively (P = 0.0055). On multivariate analysis, DR category and ypN were independently predictive of DFS. The pattern of the DR in rectal cancers after chemoradiotherapy treatment might have a prognostic value, as it likely reflects pretreatment desmoplastic environment.

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CD8+ and FOXP3+ Tumor-Infiltrating T Cells Before and After Chemoradiotherapy for Rectal Cancer

Abstract: Favorable anticancer immunity occurred after CRT for rectal cancer by altering TIL subsets. A high CD8/FOXP3 IEL ratio before CRT and a high CD8+ STL density after CRT were associated with a favorable clinical outcome.

Cited by 122 publications

References 26 publications

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

Immune Contexture, Immunoscore, and Malignant Cell Molecular Subgroups for Prognostic and Theranostic Classifications of Cancers

Immunoprofiles of colorectal cancer from Lynch syndrome

In rectal cancer, the type of desmoplastic response after preoperative chemoradiotherapy is associated with prognosis

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