Immunology of Solid Tumors Beyond Tumor-Infiltrating Lymphocytes: The Role of Tertiary Lymphoid Structures

Author(s):  
Gert G. G. M. Van den Eynden ◽  
Roberto Salgado ◽  
Karen Willard-Gallo
2019 ◽  
Vol 343 ◽  
pp. 103753 ◽  
Author(s):  
Giuseppe Badalamenti ◽  
Daniele Fanale ◽  
Lorena Incorvaia ◽  
Nadia Barraco ◽  
Angela Listì ◽  
...  

Author(s):  
Nana Zhang ◽  
Guanjun Zhang ◽  
Depu Wang ◽  
Hao Liu ◽  
Yuchi Zhang ◽  
...  

IntroductionTo explore the relationship between the tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs), and their distribution characteristics as well as the prognostic value in gastric cancer (GC).Material and methodsThe TLSs and four subtypes of TILs were assessed by immunohistochemistry (IHC) staining. The presence of MECA-79 positive high endothelial venules (HEVs) identified among the ectopic lymphocyte aggregation area in the GC tissue was defined as a valid TLSs.The number of labeled TILs were observed in 5 fields of the most positive cells in tumor center, invasive edge and within the TLSs, respectively, at a field of vision×40.ResultsThe TLSs distributed significantly higher in the tumor invasive edge than the tumor center (P <0.001). Similarly, the infiltrating density of CD8+T cells and GrB+T cells were highly distributed in the tumor infiltrating edge than the tumor center. While the total number of TILs and the FOXP3+T cells were on the contrary. There was a positive correlation between the density of TLSs and TILs either in the location or the immune phenotype. And a higher frequency of TILs and TLSs often associated with the favorable clinicopathologic parameters. Multivariate analysis revealed that the density of TILs (P= 0.019) and TLSs (P= 0.037) were the independent prognostic predictor for GC patients.ConclusionsThe formation of TLSs predicts an advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients and as a marker of efficient immunotherapies.


1995 ◽  
Vol 14 (2) ◽  
pp. 119-131 ◽  
Author(s):  
Peter S. Goedegebuure ◽  
Timothy J. Eberlein

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 917
Author(s):  
Hye Won Lee ◽  
Hyunwoo Lee ◽  
Chanho Park ◽  
Won Joon Oh ◽  
Tae Jin Kim ◽  
...  

Mixed epithelial and stromal tumor of the kidney (MESTK), a benign rare tumor with malignant transformation potential, is thought to be derived from fetal or immature cells originating from the mesonephric and Müllerian ducts. However, due to its rarity, little is known about the anti-tumor immune responses in MESTK. Herein, we present five cases of MESTK and evaluate the population of tumor-infiltrating lymphocytes (TILs) using a freshly obtained MESTK sample. Microscopically, TILs were scattered or clustered in large aggregates in the stroma in all five cases; furthermore, three cases exhibited heavy, large lymphocytic aggregates with no well-organized tertiary lymphoid structures with germinal centers. Flow cytometric analysis of TILs in one freshly obtained MESTK sample revealed that >40% of CD3+ T cells were effector memory Fas+CD28− γδ T cells expressing high levels of programmed cell death protein 1 and inducible T-cell co-stimulator, but low levels of CD44 and CD27. Most αß T cells exhibited a naïve phenotype. Additionally, we detected many activated class-switched CD21+CD27+ B cells as well as CD11chighIgMhigh marginal zone B-like and CD27−CD21−CD23− immunoglobulin (Ig)DhighIgMlow age-associated B-like cells. Collectively, for the first time, we report the immune microenvironment pattern of MESTK to oncogenic stress.


2021 ◽  
Vol 12 ◽  
Author(s):  
Na Cheng ◽  
Peng Li ◽  
Huanhuan Cheng ◽  
Xiaoxiao Zhao ◽  
Min Dong ◽  
...  

BackgroundTumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response against cancer and tertiary lymphoid structures (TLS) may contribute to lymphocytes recruitment. Both of them have been reported as potential prognostic parameters in some human malignancies. However, the roles of TILs, TLS, and their correlation in Epstein-Barr Virus-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC) are largely unknown.MethodsTo observe the correlation among TILs, TLS, and clinicopathological characteristics and their prognostic significance in EBVaGC and EBVnGC, respectively. TILs and TLS were assessed by morphology and/or immunohistochemistry, and accompanied by clinicopathological analysis from 846 gastric cancer patients in multiple institutions.ResultsForty-two (5.0%) cases of EBVaGC and 804 cases of EBVnGC were identified by in situ hybridization, respectively. For EBVnGC, higher TILs grade was correlated with TLS-present. EBVnGC patients with high TILs grade and TLS-present exhibited survival benefits. TILs (P = 0.001) and TLS (P = 0.003), especially TILs &amp; TLS (P &lt; 0.001) were independent prognostic factors in EBVnGC. A nomogram was constructed and validated for predicting the probability of overall survival and performed well with a good calibration. No significant prognostic value was detected in EBVaGC.ConclusionTILs and TLS, especially TILs &amp; TLS were promising prognostic indicators for overall survival in EBVnGC. TILs and TLS were highly overlapping in their extent and prognostic abilities, and may be considered as a coindicator of prognosis of gastric cancer. The evaluations of TILs and TLS are simple and can be assessed routinely in pathological diagnosis.


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