S2034 Combined Analysis of Lymph Node Status, Vascular Invasion, Tumor Budding and Tumor Infiltrating Lymphocytes Is Highly Predictive of Local Recurrence in Mismatch Repair-Proficient Colon Cancer

Abstract Purpose To analyze the role of programmed death ligand 1 (PD-L1) immunohistochemisty in the context of tumor microenvironment in colon cancer (CC) with focus on the interaction between tumor budding and tumor-infiltrating lymphocytes (TILs) and to elucidate its potential value for immunooncologic treatment decisions. Methods Three hundred forty seven patients with CC, stages I to IV, were enrolled. PD-L1 immunohistochemistry was performed using two different antibodies (clone 22C3 pharmDx, Agilent and clone QR1, Quartett). Tumor proportion score (TPS) as well as immune cell score (IC) was assessed. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and International TILs Working Group (ITWG). Correlation analyses as well as survival analyses were performed. Results PD-L1 positivity significantly correlated with TILs > 5% and MMR deficiency, and PD-L1-positive cases (overall and IC) showed significantly longer overall survival (OS) with both antibodies.The parameters “high grade,” “right-sidedness,” and “TILS > 5% regardless of MMR status” evolved as potential parameters for additional immunological treatment decisions. Additionally, TPS positivity correlated with low budding. More PD-L1-positive cases were seen in both high TIL groups. The low budding/high TIL group showed longer disease-free survival and longer OS in PD-L1-positive cases. Conclusion Overall, PD-L1 positivity correlated with markers of good prognosis. PD-L1 immunohistochemistry was able to identify parameters as additional potential candidates for immune therapy. Furthermore, it was able to stratify patients within the low budding/high TIL group with significant prognostic impact.

Download Full-text

Adjuvant chemotherapy in stage II and III colon cancer: the role of the “budding and TILs-(tumor-infiltrating lymphocytes) combination” as tumor-host antagonists

International Journal of Colorectal Disease ◽

10.1007/s00384-021-03896-9 ◽

2021 ◽

Author(s):

Corinna Lang-Schwarz ◽

Balint Melcher ◽

Theresa Dregelies ◽

Zahra Norouzzadeh ◽

Stefanie Rund-Küffner ◽

...

Keyword(s):

Colon Cancer ◽

Adjuvant Chemotherapy ◽

Adjuvant Treatment ◽

Tumor Infiltrating Lymphocytes ◽

Treatment Decisions ◽

Stage Ii ◽

Stage Iii ◽

Tumor Budding ◽

Stage Iii Colon Cancer ◽

Infiltrating Lymphocytes

Abstract Purpose To analyze the influence of adjuvant chemotherapy on the combination of tumor budding and tumor-infiltrating lymphocytes (TILs) in stage II and III colon cancer and to elucidate its potential value for adjuvant treatment decisions. Methods 306 patients with stage II and 205 patients with stage III colon cancer diagnosed between 2005 and 2016 who had undergone surgery in a curative setting were enrolled. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and the criteria of the International TILs Working Group (ITWG). Combinations of budding and TILs were analyzed, and the influence of adjuvant chemotherapy was assessed. Results In stage II colon cancer, stratification into the four budding/TILs groups showed no significant differences in overall survival (OS) between the chemotherapy and the surgery-alone group, not even in cases with high-risk features. In stage III colon cancer, patients with low budding/high TILs benefited significantly from chemotherapy (p=0.005). Patients with high budding/low TILs as well as high budding/high TILs showed a trend to benefit from adjuvant treatment. However, no chemotherapy benefit was seen for the low budding/low TIL group. Conclusions The budding/TIL combination identified subgroups in stage II and III colon cancer with and without benefit from adjuvant treatment. The results this study suggest that the combination of budding and TILs as tumor-host antagonists might be an additional helpful tool in adjuvant treatment decisions in stage II and III colon cancer.

Download Full-text

Predictive and Prognostic Value of BRAF and NRAS Mutation of 159 Sentinel Lymph Node Cases in Melanoma—A Retrospective Single-Institute Study

Cancers ◽

10.3390/cancers13133302 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3302

Author(s):

Gabriella Liszkay ◽

Zoltán Mátrai ◽

Kata Czirbesz ◽

Nóra Jani ◽

Eszter Bencze ◽

...

Keyword(s):

Lymph Node ◽

Sentinel Lymph Node ◽

Primary Tumor ◽

Tumor Infiltrating Lymphocytes ◽

Breslow Thickness ◽

Lymph Node Status ◽

Nras Mutation ◽

Primary Tumors ◽

Positive Slns ◽

Infiltrating Lymphocytes

Purpose: To assess the prognostic role of sentinel lymph node status (SLN) in melanoma patients, a statistical comparison was performed with the application of already known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, as well as disease outcome. Methods: Our retrospective single-center study involved 159 melanoma cases, who underwent SLN biopsy. The following clinico-pathological data were collected: age, gender, location of primary tumor, Breslow thickness, ulceration degree, histological subtype, mitosis count, lymphovascular and perineural invasion, presence of tumor-infiltrating lymphocytes, regression signs, mutations of BRAF and NRAS of the primary tumors, and SLN status. Results: From the studied clinico-pathological factors, only Breslow thickness increased the risk of SLN positivity (p = 0.025) by multivariate analysis, while neither BRAF nor NRAS mutation of the primary tumor proved to be a predictor of the SLN status. While the NRAS-mutant subgroup showed the most unfavorable outcome for progression-free and distant metastasis-free survival, their rate of positive SLNs proved to be relatively lower than that of patient groups with BRAF mutation and double-wild-type phenotypes. Conclusion: Similarly to the importance of SLN positivity, NRAS mutation of the primary tumor proved to be an independent prognostic factor of progression. Therefore, despite negative SLN, this NRAS-mutant subgroup of patients still requires closer monitoring to detect disease progression.

Download Full-text

Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma

Cancers ◽

10.3390/cancers13112689 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2689

Author(s):

Felix Popp ◽

Ingracia Capino ◽

Joana Bartels ◽

Alexander Damanakis ◽

Jiahui Li ◽

...

Keyword(s):

Pancreatic Cancer ◽

Immune Checkpoint ◽

Patient Survival ◽

Checkpoint Inhibitors ◽

Tumor Infiltrating Lymphocytes ◽

Ductal Adenocarcinoma ◽

Lymph Node Status ◽

Clinicopathologic Parameters ◽

Survival Differences ◽

Infiltrating Lymphocytes

Pancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG3, IDO, and TIM3 on tumor-infiltrating lymphocytes (TILs) and its impact on patient survival. We analyzed 153 pancreatic cancer patients from the prospectively managed database of the multicentered PANCALYZE study. Immunohistochemistry on a tissue microarray assessed VISTA, LAG3, IDO, and TIM3 expression of TILs from the patients undergoing primary resection. Complementarily, we analyzed publicly available transcriptomic data (n = 903). Successful completion of chemotherapy, and lymph node status were independent predictors of survival in the multivariate analysis of the clinicopathologic parameters. Fifteen tumors were exclusively VISTA-positive, thirteen tumors expressed VISTA together with TIM3, and ten tumors expressed VISTA together with IDO. Patients featuring tumors with high numbers of IDO-positive TILs had better patient survival (p = 0.037). VISTA, LAG3, and TIM3 expression did not correlate with survival. The analysis of publicly available data did not show survival differences. Tumors rarely co-express more than two immune molecules at the same time, and VISTA is most frequently co-expressed. Although IDO generally inhibits T-cell proliferation, a high expression of IDO was associated with improved survival. We expect immune checkpoint inhibitors against VISTA, LAG3, and TIM3 to be inefficient in a clinical application.

Download Full-text