CD8+ tumor infiltrating lymphocytes strongly correlate with molecular subtype and clinico-pathological characteristics in breast cancer patients from Sudan

Mohamed, Mahmoud; Sarwath, Hina; Salih, Nada; Bansal, Devendra; Chandra, Prem; Husain, Nazik Elmalaika; Chouchane, Lotfi; Sultan, Ali A.; Bedri, Shahinaz

doi:10.1186/s41231-016-0005-1

Cited by 5 publications

(6 citation statements)

References 39 publications

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“…Immunostaining of FFPE tissue sections was performed using the Envision Flex™ protocol on ASLink48 (Dako, Glostrup, Denmark), as described previously [ 26 ]. The antibody titers and staining parameters were optimized on recommended control tissue according to the manufacturer’s instructions (Dako, Glostrup, Denmark).…”

Section: Methodsmentioning

confidence: 99%

Introduction of p16INK4a as a surrogate biomarker for HPV in women with invasive cervical cancer in Sudan

Sarwath

Bansal

Husain

et al. 2017

Infect Agents Cancer

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BackgroundCervical cancer is the fourth most common cancer in women worldwide with highest incidence reported in Eastern Africa in 2012. The primary goal of this study was to study the expression of p16INK4a in squamous cell carcinoma (SCC) of the cervix by immunohistochemistry (IHC) and determine relation with clinico-pathological parameters. This study further explored the correlation of p16INK4a immunostaining with another proliferation marker, Ki-67 and to study if human papillomavirus (HPV) IHC can be used as a marker for detection of virus in high-grade dysplasia.MethodsA total of 90 samples, diagnosed for cervical cancer, were included in the study. Fixed Paraffin Embedded (FFPE) tissue sections were stained with anti-p16INK4a, anti-Ki-67 and anti-HPV antibodies using automated immunohistochemistry platform (ASLink 48-DAKO).ResultsImmunohistochemical protein expression of p16INK4a positivity was found to be highest in SCC (92.2%, n = 71) than other HPV tumors (76.9%, n = 10). The majority of cases (97.4%) were p16INK4a positive in the age group 41–60 years. In addition, a statistically significant difference between p16INK4a and HPV was observed among total cervical tumor cases and SCC cases.ConclusionsAs expected staining of invasive cervical cancer with anti-HPV showed rare positivity because HPV heralds active infection in dysplastic lesions and not of frank cervical carcinoma. In contrast, anti-p16INK4a IHC results showed positive correlation in SCC and other cervical tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-017-0159-0) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Introduction of p16INK4a as a surrogate biomarker for HPV in women with invasive cervical cancer in Sudan

Sarwath

Bansal

Husain

et al. 2017

Infect Agents Cancer

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“…Their data supported the hypothesis that breast cancer is immunogenic and might be targetable by immune-modulating therapies. Mohamed et al 62 reported HER2/neu-positive breast cancer had a significantly higher CD8 þ content (26.1%) compared to luminal A (13.5%), luminal B (17.0%), or TNBC (14.5%). This, however, did not apply to CD3 þ or CD45RO þ type cells, and there was no significant correlation between CD45RO þ TILs and clinicopathologic parameters.…”

Section: Immune Cells In Invasive Carcinoma Of the Breastmentioning

confidence: 99%

“…TLS are generally associated with tumors with a more aggressive phenotype such as high-grade tumors, TNBC, and HER2 þ tumors. 62,65,66 Liu et al 65 reported TLS were associated with higher tumor grade, apocrine phenotype, necrosis, extensive in-situ component, lymphovascular invasion, high TIL, HR negativity, HER2 positivity, and c-kit expression. A favorable impact of TLS density on overall survival (OS) and disease-free survival (DFS) of patients has been observed.…”

Section: Nature Of Immune Cells In Tertiary Lymph Structures In Breastmentioning

confidence: 99%

“…A favorable impact of TLS density on overall survival (OS) and disease-free survival (DFS) of patients has been observed. 62,63,[66][67][68][69][70][71] An important component of TLS are HEV. These are specialized postcapillary venules found in lymphoid tissues that support high levels of lymphocyte extravasation from the blood.…”

Section: Nature Of Immune Cells In Tertiary Lymph Structures In Breastmentioning

confidence: 99%

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The Role of Immune Cells in Breast Tissue and Immunotherapy for the Treatment of Breast Cancer

Goff

Danforth

2021

Clinical Breast Cancer

141

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Immune cells are present in normal breast tissue and in breast carcinoma. The nature and distribution of the immune cell subtypes in these tissues are reviewed to promote a better understanding of their important role in breast cancer prevention and treatment. We conducted a review of the literature to define the type, location, distribution, and role of immune cells in normal breast tissue and in in situ and invasive breast cancer. Immune cells in normal breast tissue are located predominantly within the epithelial component in breast ductal lobules. Immune cell subtypes representing innate immunity (NK, CD68 þ , and CD11c þ cells) and adaptive immunity (most commonly CD8 þ , but CD4 þ and CD20 þ as well) are present; CD8 þ cells are the most common subtype and are primarily effector memory cells. Immune cells may recognize neoantigens and endogenous and exogenous ligands and may serve in chronic inflammation and immunosurveillance. Progression to breast cancer is characterized by increased immune cell infiltrates in tumor parenchyma and stroma, including CD4 þ and CD8 þ granzyme B þ cytotoxic T cells, B cells, macrophages and dendritic cells. Tumor-infiltrating lymphocytes in breast cancer may serve as prognostic indicators for response to chemotherapy and for survival. Experimental strategies of adoptive transfer of breast tumor-infiltrating lymphocyte may allow regression of metastatic breast cancer and encourage development of innovative T-cell strategies for the immunotherapy of breast cancer. In conclusion, immune cells in breast tissues play an important role throughout breast carcinogenesis. An understanding of these roles has important implications for the prevention and the treatment of breast cancer.

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“…The PDGFRa and -b antibodies have been validated and described previously and cross-detection of the two related receptors has been excluded 33,36 . The ASMA 39,[63][64][65] , CD90 66,67 , FAP 54,68 and CD8a 65,69,70 antibodies are widely used in IHC by several groups and have been published previously. Cross-reactivity of these antibodies has been validated by Western Blot analysis by the manufacturers and all antibodies are recommended for IHC according to the manufacturer's datasheet.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Fibroblasts in urothelial bladder cancer define stroma phenotypes that are associated with clinical outcome

Mezheyeuski

Segersten

Leiss

et al. 2020

Sci Rep

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Little attention was given to the interaction between tumor and stromal cells in urothelial bladder carcinoma (UBC). While recent studies point towards the existence of different fibroblast subsets, no comprehensive analyses linking different fibroblast markers to UBC patient survival have been performed so far. Through immunohistochemical analysis of five selected fibroblast markers, namely alpha smooth muscle actin (ASMA), CD90/Thy-1, fibroblast activation protein (FAP), platelet derived growth factor receptor-alpha and-beta (PDGFRa,-b), this study investigates their association with survival and histopathological characteristics in a cohort of 344 UBC patients, involving both, muscleinvasive and non-muscle-invasive cases. The data indicates that combinations of stromal markers are more suited to identify prognostic patient subgroups than single marker analysis. Refined stromamarker-based patient stratification was achieved through cluster analysis and identified a FAPdominant patient cluster as independent marker for shorter 5-year-survival (HR(95% CI)2.25(1.08-4.67), p = 0.030). Analyses of interactions between fibroblast and CD8a-status identified a potential minority of cases with CD90-defined stroma and high CD8a infiltration showing a good prognosis of more than 80% 5-year-survival. Presented analyses point towards the existence of different stroma-cell subgroups with distinct tumor-modulatory properties and motivate further studies aiming to better understand the molecular tumor-stroma crosstalk in UBC. The estimated incidence of urinary bladder cancer (UBC) worldwide was about 550.000 new cases and 200.000 deaths in 2018 1 , with highest incidences indicated in developed areas 2. Given that the prevalence of UBC is several times higher than the incidence, it represents a major burden for health care systems. Carcinomas originating from the urothelium, the inner surface of the bladder, represent the most common type of bladder cancer 3,4. Approximately 70% of all newly diagnosed cases are classified as non-muscle-invasive bladder cancer disease, while about 30% of patients have already muscle-invasive tumors with 10-15% of them being metastatic 5-8. Reported 5-year recurrence rates of non-muscle invasive cases range between 40-70% among the highest recurrence rates of solid tumors 3,9. Multidisciplinary approaches have been established in order to improve patient management and to decrease the mortality rate, but still treatment strategies for UBC remain controversial. A better understanding of the mechanisms underlying tumor progression is crucial and novel prognostic and predictive markers as well as therapeutic targets need to be identified 10,11. Recent research efforts on UBC aimed mostly to decipher molecular drivers of an invasive tumor phenotype through description of genetic varieties, and with the introduction of checkpoint inhibitory immunotherapy, awareness has also risen for tumor infiltrating leukocytes 12,13. However, little attention was given the interaction of tumor cells and non-leukoc...

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CD8+ tumor infiltrating lymphocytes strongly correlate with molecular subtype and clinico-pathological characteristics in breast cancer patients from Sudan

Cited by 5 publications

References 39 publications

Introduction of p16INK4a as a surrogate biomarker for HPV in women with invasive cervical cancer in Sudan

Introduction of p16INK4a as a surrogate biomarker for HPV in women with invasive cervical cancer in Sudan

The Role of Immune Cells in Breast Tissue and Immunotherapy for the Treatment of Breast Cancer

Fibroblasts in urothelial bladder cancer define stroma phenotypes that are associated with clinical outcome

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