Effect of tumor budding and tumor infiltrating lymphocytes on prognosis of colorectal mucinous adenocancers

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.

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The prognostic significant of tumor budding, tumor stroma ratio and tumor-infiltrating lymphocytes in gallbladder adenocarcinoma

Journal of Contemporary Medicine ◽

10.16899/jcm.1033380 ◽

2022 ◽

Vol 12 (2) ◽

pp. 1-1

Author(s):

İlke Evrim SEÇİNTİ ◽

Didar GÜRSOY ◽

Tümay ÖZGÜR ◽

Emre DİRİCAN ◽

Muhyittin TEMİZ

Keyword(s):

Tumor Infiltrating Lymphocytes ◽

Tumor Stroma ◽

Tumor Budding ◽

Gallbladder Adenocarcinoma ◽

Infiltrating Lymphocytes

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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

Gastroenterology ◽

10.1016/s0016-5085(08)61404-3 ◽

2008 ◽

Vol 134 (4) ◽

pp. A-301

Author(s):

Inti Zlobec ◽

Kristi Baker ◽

Parham Minoo ◽

Luigi Terracciano ◽

Alessandro Lugli

Keyword(s):

Colon Cancer ◽

Lymph Node ◽

Local Recurrence ◽

Mismatch Repair ◽

Vascular Invasion ◽

Tumor Infiltrating Lymphocytes ◽

Tumor Budding ◽

Lymph Node Status ◽

Combined Analysis ◽

Infiltrating Lymphocytes

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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.

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Tumor-infiltrating lymphocytes and tumor budding refine prognostication in patients with low- and high-risk stage III colon cancers (NCCTG N0147)[Alliance].

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4065 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4065-4065

Author(s):

Dan Sha ◽

Hee Eun Lee ◽

Nathan R. Foster ◽

Qian Shi ◽

Steven R Alberts ◽

...

Keyword(s):

High Risk ◽

Adjuvant Chemotherapy ◽

Tumor Infiltrating Lymphocytes ◽

Low Risk ◽

Stage Iii ◽

Tumor Budding ◽

Relative Contribution ◽

Kras Status ◽

Risk Patients ◽

Infiltrating Lymphocytes

4065 Background: Tumor infiltrating lymphocytes (TILs) and tumor budding (linked to epithelial mesenchymal transition) may influence metastatic potential and patient prognosis. We analyzed these features and their relative contribution to survival among low (T1-3 N1) and high (T4 and/or N2) risk groups, defined by the IDEA study, used to inform the duration of adjuvant chemotherapy in stage III colon cancer. Methods: Among 1,532 patients (low risk n=804; high risk n=728) treated in a phase III adjuvant trial of FOLFOX + cetuximab (x 6 months), intraepithelial TIL densities and tumor budding were quantified at microscopy in routine histologic sections. Optimal cutpoints were determined in association with 5-yr disease-free survival (DFS). Relative contribution of variables to DFS was calculated using χ2 from Harrell’s rms R package based on multivariable Cox regression models. Results: In the overall cohort, the tumor budding/TILs combined variable was more robust for predition of DFS than either alone. Budding/TILs was significantly associated with DFS in both low (HRadj, 1.59; 95% CI, 1.02-2.48; p=.0273) and high (HRadj, 2.82; 95% CI, 1.72-4.63; p<.0001) risk patients. We then determined its relative contribution (%) to DFS (Table). Among low risk, budding/TILs ranked second (24.4%) behind KRAS status (45.5%) and ahead of treatment arm (7.2%) and mismatch repair (MMR) status (6.1%). Among high risk, budding/TILs contributed the most to DFS (45.4%) followed by primary tumor sidedness (13.0%), performance status (12.0%), and MMR (10.4%). Conclusions: Tumor budding/TILs provides robust prognostic stratification by risk group to improve anatomic tumor staging. The relative contribution of budding/TILs to DFS was second only to KRAS status in low risk patients, and was the most important predictor of DFS in high risk patients. Evaluation in patients treated with 3 vs 6 mos of adjuvant chemotherapy is warranted. [Table: see text]

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