Comprehensive Analysis of Tumor Microenvironment and PD-L1 Expression Associations with Clinicopathological Features and Prognosis in Diffuse Large B-Cell Lymphoma

The tumor microenvironments (TME) of diffuse large B-cell lymphoma (DLBCL) subgroups have remained poorly characterized. Here, we dissected the composition and spatial organization of the TME in germinal center B-cell (GCB), activated B-cell (ABC), and testicular (T-) DLBCL using gene expression profiling and multiplex immunohistochemistry. We found that high proportions of M2-like tumor-associated macrophages (TAM) and cytotoxic tumor-infiltrating T cells (TIL) were characteristic of ABC DLBCL TME. Furthermore, high CD8+ TIL content translated to favorable outcomes. In contrast, GCB DL-BCL TME was enriched in CD4+ TIL, regulatory TIL, and a higher M1-like : M2-like TAM ratio, and high proportions of TAM and Granzyme B+ cells associated with worse survival. TIL and TAM interacted more frequently with M2-like TAM and cytotoxic TIL in the ABC DLBCL in contrast to GCB subtype, where the interactions were more abundant with other TIL and CD4+ TIL. In T-DLBCL, TME resembled that of ABC DLBCL with a higher proportion of M2-like TAM and cytotoxic cells, except that checkpoint-positive TIL were less prominent compared to DLBCL NOS. Cytotoxic TIL also interacted more with TIL and TAM. A large number of CD163+ TAM interactions with distinct TIL translated to unfavorable survival both in GCB DLBCL and T-DLBCL, whereas a high number of interactions between TIL and TAM, CD4+ TIL and TAM, and CD4+ TIL and other TIL were associated with favorable outcomes only in T-DLBCL. Together, our data demonstrate biologically and clinically relevant differences in the composition of and cellular interactions in the TME between various DLBCL entities.

A phase II trial of AZD1152 in relapsed/refractory diffuse large B-cell lymphoma.

Correlation of Toll-like Receptor (TLR) and PD-1 Pathways in Central Nervous System Lymphoma: A Clinicopathological Study on Outcomes

Impact of Tumor Infiltrating T Cells in Patients with Diffuse Large B-Cell Lymphoma

Prognostic Relevance of Tumor-Infiltrating T-Lymphocytes on Total Metabolic Tumor Volume-Based Risk Stratification of Patients with Diffuse Large B-Cell Lymphoma

Infused Autograft-Absolute Lymphocyte Count Predicts Superior Survival in Diffuse Large B-Cell Lymphoma Patients Post-Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation: A Matched-Control Study

Objective This study aimed to compare the clinical characteristics and prognoses of primary Waldeyer's ring diffuse large B-cell lymphoma (DLBCL) and extranodal nasal-type NK/T-cell lymphoma ( ENKTCL).Methods From 2000 to 2008,122 patients with primary Waldeyer's ring DLBCL and 44 patients with primary Waldeyer' s ring ENKTCL consecutively diagnosed were retrospectively compared.Patients with DLBCL usually received 4-6 cycles of CHOP-based chemotherapy followed by involved-field radiotherapy.Patients with early stage ENKTCL usually received extended-field radiotherapy with or without subsequent chemotherapy,or short courses ( 1 - 3 cycles ) of chemotherapy followed by radiotherapy.Kaplan-Meier method was used for survival analysis.Logrank method was used for univariate analysis.Results The follow-up rate was 82％.The number of patients followed 5 years were 32 and 15 in DLBCL and ENKTCL.DLBCL mainly presented with stage Ⅱ tonsillar disease with regional lymph node involvement.ENKTCL occurred predominately in young males,as nasopharyngeal stage I disease with B symptoms and involving adjacent structures.The 5-year overall survival (OS) and progression-free survival (PFS) rates were 74％ and 67％ in DLBCL,and 68％ and 59％ in ENKTCL (x2=0.53,1.06,P=0.468,0.303),respectively.In stage Ⅰ and Ⅱ diseases,the 5-year OS and PFS rates were 79％ and 76％ for DLBCL compared to 72％ and 62％ for ENKTCL (x2 =1.20,2.46,P=0.273,0.117).On univariate analysis,age ＞ 60 years,elevated lactate dehydrogenase,eastern cooperative oncology group performance status ＞ 1,international prognosis index ( IPI ) score ≥ 1,stage Ⅲ/Ⅳ diseases and bulky disease were associated with unfavorable survival for DLBCL (x2=9.40,12.72,6.15,10.36,12.48,5.53,P=0.002,0.000,0.013,0.001,0.000,0.019),and only age＞60 years and IPI score ≥ 1 were associated with poor survival for ENKTCL (x2 =3.98,8.41,P =0.046,0.004).Conclusions These results indicate that remarkable clinical disparities exist between DLBCL and ENKTCL in Waldeyer's ring. Different treatment strategies for each can result in similarly favorable prognoses. Key words: Lymphoma,diffuse large B-cell,Waldeyer's ring/radiotherapy; Lymphoma,diffuselarge B-cell,Waldeyer's nng/chemotherapy; Lymphoma,extranodal nasal-type NK/T-cell,Waldeyer's ring/radiotherapy; Lymphoma,extranodal nasal-type NK/T-cell,Waldeyer's ring/cheomotherapy; Prognosis

Type 2 Diabetes Mellitus Strongly Impacts Survival in Patients with Diffuse Large B Cell Lymphoma

Frontmind: A Phase III, Multicenter, Randomized, Double-Blind Study of Tafasitamab + Lenalidomide + R-CHOP Versus R-CHOP Alone for Newly Diagnosed High-Intermediate and High-Risk Diffuse Large B-Cell Lymphoma

The Presence of Pleural Effusion at Diagnosis Predicts Poor Outcomes in Diffuse Large B-Cell Lymphoma Patients with MYC -Rearrangement or Double Protein Expression

AimTo investigate the correlation between clinicopathological features and risk stratification in cervical cancer patients, and evaluate the feasibility of tumor-infiltrating immune cells as prognostic biomarkers in clinical practice.MethodsCD3+ tumor infiltrating T cells (TILs), CD45RO+ TILs, CD4+ TILs, CD8+ TILs, FOXP3+ TILs (regulatory T cells, Tregs), CD68+ tumor associated macrophages (TAMs), CD163+ TAMs, and PD-L1+ tumor cells were immunostained in formalin-fixed paraffin-embedded (PPFE) tissues from 96 cervical cancer patients. Immunostaining density and other clinicopathological features such as age, FIGO stage, histopathologic type, Ki67 index, HPV status, lymhovasular invasion status (LVI), lymph node metastasis, tumor size, stromal invasion status, surgical margin status, and parametrial invasion, were evaluated for their roles in risk stratification of cervical cancer patients.ResultsThe results showed that significant differences of lymph node metastasis (p = 0.003), surgical margin status (p = 0.020), and stromal invasion status (p = 0.004) existed between lVI(−) and LVI(+) patients. CD3+ TILs in the central tumor area (p = 0.010), CD4+ TILs in the central tumor area (p = 0.045), CD8 + TILs in the central tumor area (p = 0.033), and CD8+ TILs in the invasive margin area (p = 0.004) showed significant differences between lVI(−) and LVI(+) patients. When patients were grouped by status of lymph node metastasis, significant differences of FIGO stage (p = 0.005), LVI status (p = 0.003), CD3+ TILs in the central tumor area (p = 0.045), CD45RO+ TILs in the central tumor area (p = 0.033), and CD45RO+ TILs in the invasive margin area (p = 0.028) were also observed. After the patients were stratified into low-, intermediate-, and high risk groups, significant differences of FIGO stage (p = 0.018), status of lymph node metastasis (p = 0.000), LVI status (p = 0.000), parametrial invasion status (p=0.012), stromal invasion status (p = 0.000), tumor growth pattern (p = 0.015) and tumor size (p = 0.000) were identified among 3 groups of patients, while only CD45RO+ TILs in the invasive margin area (p = 0.018) and FOXP3+ TILs in the central tumor area (p = 0.009) were statistically different among three groups of patients. Spearman’s correlation analysis demonstrated that FIGO stage, LVI status, status of lymph node metastasis, parametrial invasion, stromal invasion status, and tumor size positively correlated with risk stratification (P = 0.005, 0.020, 0.000, 0.022, 0.000, and 0.000 respectively), while CD45RO+ TILs in the invasive margin area and FOXP3+ TILs in the central tumor area showed statistically negative correlation with risk stratification (P = 0.031, 0.009 respectively).ConclusionOur study suggested that CD45RO+ TILs in the invasive margin area and FOXP3+ TILs in the central tumor area might be useful biomarkers for risk stratification in cervical cancer patients. Large cohort studies of cervical cancer patients are required to validate our hypothesis.

Increased Activity of the S Phase Kinase Cdc7 Is Associated with Poor Outcome in Diffuse Large B Cell Lymphoma (DLBCL).

Clinical Significance of PD-1 and PD-L1 Expression and Ongoing Interaction in the Tumor Microenvironment in Diffuse Large B Cell Lymphoma (DLBCL) Treated with R-CHOP

The Host Genetic Background of DNA Repair Mechanisms Represents An Independent Predictor of Progression and Survival in Diffuse Large B-Cell Lymphoma Treated with R-CHOP.

High Amount of PD-L1+ Tumor Associated Macrophages Is Associated with Better Survival in Patients with Primary Testicular Lymphoma