Cumulative suppressive index as a predictor of relapse free survival and overall survival in <scp>Human Papilloma Virus</scp>‐negative oral squamous cell carcinomas with negative resection margins

Background Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor. Methods Tissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (< 150 µm from the tumor center, TF) and peritumoral region (≥ 150 µm from the tumor center, PT) was evaluated via comparison. The expression of CD68 and CD163 in different regions was further analyzed based on the cell colocalization method. In addition, different immune phenotypes were studied and compared according to the degree of CD8 infiltration. Results The expression trends of 12 markers in the TF and TC regions were basically the same in the primary tumor and liver metastasis lesions. However, in comparison of the TF and PT regions, the expression trends were not identical between primary and liver metastases, especially CD163, which was more highly expressed in the PT region relative to the TF region. In the contrast of different space distribution, the expression of CD163 was higher in liver metastases than in the primary foci. Further analysis of CD68 and CD163 via colocalization revealed that the distribution of macrophages in liver metastases was significantly different from that in the primary foci, with CD68−CD163+ macrophages predominating in liver metastases. In addition, among the three immunophenotypes, CD163 expression was highest in the immune rejection phenotype. Conclusions The immune cells found in the primary tumors of colorectal cancer differed from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells were present in the liver metastases, with the most pronounced differential distribution found for macrophages. CD68−CD163+ macrophages may be associated with intrahepatic immunosuppression and weak immunotherapeutic effects.

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“…1 A right). On this basis, all immune cell infiltrations are counted as cell count/mm 2 of regional tissue area (density) [ 23 , 24 ].…”

Section: Methodsmentioning

confidence: 99%

Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Han

Fan

et al. 2022

J Transl Med

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“…Stratification of patients based on immune characteristics was further extended to include also immune modulatory molecules. For example, a prognostic score as suppressive index for HNSCC was established by combining strong predictors for the survival of these patients, such as the abundance, location and spatial pattern of TILs to other immune markers, like expression of the human leukocyte antigen (HLA) class I ( 45 , 46 ). However, not only the quantity, but also the quality of TILs is an important factor for patients’ outcome.…”

Section: Immune Cell Repertoire In the Tme And Its Clinical Relevancementioning

confidence: 99%

Modulation of Lymphocyte Functions in the Microenvironment by Tumor Oncogenic Pathways

Seliger

Massa

2022

Front. Immunol.

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Despite the broad application of different immunotherapeutic strategies for the treatment of solid as well as hematopoietic cancers, the efficacy of these therapies is still limited, with only a minority of patients having a long-term benefit resulting in an improved survival rate. In order to increase the response rates of patients to the currently available immunotherapies, a better understanding of the molecular mechanisms underlying the intrinsic and/or extrinsic resistance to treatment is required. There exist increasing evidences that activation of different oncogenic pathways as well as inactivation of tumor suppressor genes (TSG) in tumor cells inhibit the immune cell recognition and influegnce the composition of the tumor microenvironment (TME), thus leading to an impaired anti-tumoral immune response. A deeper understanding of the link between the tumor milieu and genomic alterations of TSGs and oncogenes is indispensable for the optimization of immunotherapies and to predict the patients’ response to these treatments. This review summarizes the role of different cancer-related, oncogene- and TSG-controlled pathways in the context of anti-tumoral immunity and response to different immunotherapies.

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“…After automatic fluorescence background was removed, tissue segmentation, cell segmentation, and signal threshold processing are performed on 3 regions: tumor center (TC), tumor invasive front (less than 150 µm from the tumor center, TF) and peritumor (more than or equal to 150 µm from the tumor center, PT) (Figure 1A right). On this basis, all immune cell infiltrations are counted as cell count/mm² of regional tissue area (density) (23,24).…”

Section: Imaging Acquisition and Analysismentioning

confidence: 99%

Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Fan

et al. 2022

Preprint

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Background Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor. Methods Tissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (<150 µm from the tumor center, TF) and peritumoral region (≥150 µm from the tumor center, PT) was evaluated via comparison. The expression of CD68 and CD163 in different regions was further analyzed based on the cell colocalization method. In addition, different immune phenotypes were studied and compared according to the degree of CD8 infiltration.Results The expression trends of 12 markers in the TF and TC regions were basically the same in the primary tumor and liver metastasis lesions. However, in comparison of the TF and PT regions, the expression trends were not identical between primary and liver metastases, especially CD163, which was more highly expressed in the PT region relative to the TF region. In the contrast of different space distribution, the expression of CD163 was higher in liver metastases than in the primary foci. Further analysis of CD68 and CD163 via colocalization revealed that the distribution of macrophages in liver metastases was significantly different from that in the primary foci, with CD68-CD163+ macrophages predominating in liver metastases. In addition, among the three immunophenotypes, CD163 expression was highest in the immune rejection phenotype. Conclusions The immune cells found in the primary tumors of colorectal cancer differed from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells were present in the liver metastases, with the most pronounced differential distribution found for macrophages. CD68-CD163+ macrophages may be associated with intrahepatic immunosuppression and weak immunotherapeutic effects.

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Cumulative suppressive index as a predictor of relapse free survival and overall survival in Human Papilloma Virus‐negative oral squamous cell carcinomas with negative resection margins

Cited by 5 publications

References 19 publications

Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

Modulation of Lymphocyte Functions in the Microenvironment by Tumor Oncogenic Pathways

Multi-perspective comparison of the immune microenvironment of primary colorectal cancer and liver metastases

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