Tumor Infiltrating Lymphocytes As an Endpoint in Cancer Vaccine Trials

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Mar 24

PMID 36960052

Authors

Patrick M McCarthy

Franklin A Valdera

Todd R Smolinsky

Alexandra M Adams

Anne E OShea

Katryna K Thomas

Spencer Van Decar

Elizabeth L Carpenter

Ankur Tiwari

John W Myers

Diane F Hale

Timothy J Vreeland

George E Peoples

Alex Stojadinovic

Guy T Clifton

Affiliations

Soon will be listed here.

Abstract

Checkpoint inhibitors have invigorated cancer immunotherapy research, including cancer vaccination. Classic early phase trial design and endpoints used in developing chemotherapy are not suited for evaluating all forms of cancer treatment. Peripheral T cell response dynamics have demonstrated inconsistency in assessing the efficacy of cancer vaccination. Tumor infiltrating lymphocytes (TILs), reflect the local tumor microenvironment and may prove a superior endpoint in cancer vaccination trials. Cancer vaccines may also promote success in combination immunotherapy treatment of weakly immunogenic tumors. This review explores the impact of TILs as an endpoint for cancer vaccination in multiple malignancies, summarizes the current literature regarding TILs analysis, and discusses the challenges of providing validity and a standardized implementation of this approach.

Citing Articles

Unlocking the Microbial Symphony: The Interplay of Human Microbiota in Cancer Immunotherapy Response.

Chacon J, Faizuddin F, McKee J, Sheikh A, Vasquez Jr V, Gadad S Cancers (Basel). 2025; 17(5).

PMID: 40075661 PMC: 11899421. DOI: 10.3390/cancers17050813.

From silent partners to potential therapeutic targets: macrophages in colorectal cancer.

Khizar H, Ali K, Wang J Cancer Immunol Immunother. 2025; 74(4):121.

PMID: 39998578 PMC: 11861851. DOI: 10.1007/s00262-025-03965-w.

Nanostructured lipid carriers based mRNA vaccine leads to a T cell-inflamed tumour microenvironment favourable for improving PD-1/PD-L1 blocking therapy and long-term immunity in a cold tumour model.

Fournier C, Mercey-Ressejac M, Derangere V, Al Kadi A, Rageot D, Charrat C EBioMedicine. 2025; 112:105543.

PMID: 39793480 PMC: 11774803. DOI: 10.1016/j.ebiom.2024.105543.

Unlocking cancer vaccine potential: What are the key factors?.

Grant M, Ni Lee L, Chinnakannan S, Tong O, Kwok J, Cianci N Hum Vaccin Immunother. 2024; 20(1):2331486.

PMID: 38564321 PMC: 11657071. DOI: 10.1080/21645515.2024.2331486.

References

Abraham A, Al-Refaie W, Parsons H, Dudeja V, Vickers S, Habermann E . Disparities in pancreas cancer care. Ann Surg Oncol. 2013; 20(6):2078-87. DOI: 10.1245/s10434-012-2843-z. View

Neu K, Tang Q, Wilson P, Khan A . Single-Cell Genomics: Approaches and Utility in Immunology. Trends Immunol. 2017; 38(2):140-149. PMC: 5479322. DOI: 10.1016/j.it.2016.12.001. View

Levy-Jurgenson A, Tekpli X, Kristensen V, Yakhini Z . Spatial transcriptomics inferred from pathology whole-slide images links tumor heterogeneity to survival in breast and lung cancer. Sci Rep. 2020; 10(1):18802. PMC: 7606448. DOI: 10.1038/s41598-020-75708-z. View

Lutz E, Wu A, Bigelow E, Sharma R, Mo G, Soares K . Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol Res. 2014; 2(7):616-31. PMC: 4082460. DOI: 10.1158/2326-6066.CIR-14-0027. View

Cipponi A, Mercier M, Seremet T, Baurain J, Theate I, van den Oord J . Neogenesis of lymphoid structures and antibody responses occur in human melanoma metastases. Cancer Res. 2012; 72(16):3997-4007. DOI: 10.1158/0008-5472.CAN-12-1377. View

Chiossone L, Dumas P, Vienne M, Vivier E . Natural killer cells and other innate lymphoid cells in cancer. Nat Rev Immunol. 2018; 18(11):671-688. DOI: 10.1038/s41577-018-0061-z. View

Shen Z, Zhou S, Wang Y, Li R, Zhong C, Liang C . Higher intratumoral infiltrated Foxp3+ Treg numbers and Foxp3+/CD8+ ratio are associated with adverse prognosis in resectable gastric cancer. J Cancer Res Clin Oncol. 2010; 136(10):1585-95. DOI: 10.1007/s00432-010-0816-9. View

Berry J, Vreeland T, Trappey A, Hale D, Peace K, Tyler J . Cancer vaccines in colon and rectal cancer over the last decade: lessons learned and future directions. Expert Rev Clin Immunol. 2016; 13(3):235-245. DOI: 10.1080/1744666X.2016.1226132. View

Bai Z, Zhou Y, Ye Z, Xiong J, Lan H, Wang F . Tumor-Infiltrating Lymphocytes in Colorectal Cancer: The Fundamental Indication and Application on Immunotherapy. Front Immunol. 2022; 12:808964. PMC: 8795622. DOI: 10.3389/fimmu.2021.808964. View

10.

Turksma A, Coupe V, Shamier M, Lam K, de Weger V, Belien J . Extent and Location of Tumor-Infiltrating Lymphocytes in Microsatellite-Stable Colon Cancer Predict Outcome to Adjuvant Active Specific Immunotherapy. Clin Cancer Res. 2015; 22(2):346-56. DOI: 10.1158/1078-0432.CCR-13-2462. View

11.

Hodi F, Butler M, Oble D, Seiden M, Haluska F, Kruse A . Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A. 2008; 105(8):3005-10. PMC: 2268575. DOI: 10.1073/pnas.0712237105. View

12.

Dieu-Nosjean M, Antoine M, Danel C, Heudes D, Wislez M, Poulot V . Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol. 2008; 26(27):4410-7. DOI: 10.1200/JCO.2007.15.0284. View

13.

Chiou V, Burotto M . Pseudoprogression and Immune-Related Response in Solid Tumors. J Clin Oncol. 2015; 33(31):3541-3. PMC: 4622096. DOI: 10.1200/JCO.2015.61.6870. View

14.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

15.

Tan W, Nerurkar S, Cai H, Ng H, Wu D, Wee Y . Overview of multiplex immunohistochemistry/immunofluorescence techniques in the era of cancer immunotherapy. Cancer Commun (Lond). 2020; 40(4):135-153. PMC: 7170662. DOI: 10.1002/cac2.12023. View

16.

Small E, Schellhammer P, Higano C, Redfern C, Nemunaitis J, Valone F . Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006; 24(19):3089-94. DOI: 10.1200/JCO.2005.04.5252. View

17.

Harrop R, Connolly N, Redchenko I, Valle J, Saunders M, Ryan M . Vaccination of colorectal cancer patients with modified vaccinia Ankara delivering the tumor antigen 5T4 (TroVax) induces immune responses which correlate with disease control: a phase I/II trial. Clin Cancer Res. 2006; 12(11 Pt 1):3416-24. DOI: 10.1158/1078-0432.CCR-05-2732. View

18.

Koopman M, Kortman G, Mekenkamp L, Ligtenberg M, Hoogerbrugge N, Antonini N . Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009; 100(2):266-73. PMC: 2634718. DOI: 10.1038/sj.bjc.6604867. View

19.

Sinicrope F, Rego R, Ansell S, Knutson K, Foster N, Sargent D . Intraepithelial effector (CD3+)/regulatory (FoxP3+) T-cell ratio predicts a clinical outcome of human colon carcinoma. Gastroenterology. 2009; 137(4):1270-9. PMC: 2873775. DOI: 10.1053/j.gastro.2009.06.053. View

20.

Stubbington M, Rozenblatt-Rosen O, Regev A, Teichmann S . Single-cell transcriptomics to explore the immune system in health and disease. Science. 2017; 358(6359):58-63. PMC: 5654495. DOI: 10.1126/science.aan6828. View