Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

Our plain-English summary of Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors, by S. Hendry, R. Salgado, T. Gevaert, et al (Advances in Anatomic Pathology, 2017).

The study

• Authors: S. Hendry, R. Salgado, T. Gevaert, P.A. Russell, T. John, B. Thapa, M. Christie, K. van de Vijver, M.V. Estrada, P.I. Gonzalez-Ericsson, M. Sanders, B. Solomon, C. Solinas, G.G.G.M. Van den Eynden, Y. Allory, M. Preusser, J. Hainfellner, G. Pruneri, A. Vingiani, S. Demaria, F. Symmans, P. Nuciforo, L. Comerma, E.A. Thompson, S. Lakhani, S.R. Kim, S. Schnitt, C. Colpaert, C. Sotiriou, S.J. Scherer, M. Ignatiadis, S. Badve, R.H. Pierce, G. Viale, N. Sirtaine, F. Penault-Llorca, T. Sugie, S. Fineberg, S. Paik, A. Srinivasan, A. Richardson, Y. Wang, E. Chmielik, J. Brock, D.B. Johnson, J. Balko, S. Wienert, V. Bossuyt, S. Michiels, N. Ternes, N. Burchardi, S.J. Luen, P. Savas, F. Klauschen, P.H. Watson, B.H. Nelson, C. Criscitiello, S. O'Toole, D. Larsimont, R. de Wind, G. Curigliano, F. André, M. Lacroix-Triki, M. van de Vijver, F. Rojo, G. Floris, S. Bedri, J. Sparano, D. Rimm, T. Nielsen, Z. Kos, S. Hewitt, B. Singh, G. Farshid, S. Loibl, K.H. Allison, N. Tung, S. Adams, K. Willard-Gallo, H.M. Horlings, L. Gandhi, A. Moreira, F. Hirsch, M.V. Dieci, M. Urbanowicz, I. Brcic, K. Korski, F. Gaire, H. Koeppen, A. Lo, J. Giltnane, M.C. Rebelatto, K.E. Steele, J. Zha, K. Emancipator, J.W. Juco, C. Denkert, J. Reis-Filho, S. Loi, S.B. Fox
• Journal: Advances in Anatomic Pathology
• Published: 2017;24(6):311-335
• Type of article: Review
• Cited by: 652 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

In plain English

This article was a review, the second of two parts, by the International Immuno-Oncology Biomarkers Working Group. It does not mention asbestos. It surveyed published research on tumor-infiltrating lymphocytes (TILs), which are lymphocytes (a type of immune cell) within tumors, in melanoma and gastrointestinal, lung, gynecologic, head and neck, genitourinary and brain tumors. It discussed adapting the group's proposed standard TIL-scoring method to these tumors, noting it may not suit some, such as gliomas. Mesothelioma took up one paragraph. The authors wrote that less is known about the immune environment of pleural malignant mesothelioma, and that early immunohistochemical studies suggested TILs were linked to a better outlook. They also described unpublished work, given as a personal communication, on 329 pleural malignant mesothelioma cases. In that work, the stromal TILs score was strongly negatively correlated with survival, while the presence of tertiary lymphoid structures (organized clusters of immune cells) was independently associated with better survival. The authors concluded that their methods should be treated as a tool for further research. They acknowledged that the method has limitations and many open questions remain.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review (part 2 of a two-part review) of published literature on tumor-infiltrating lymphocytes, with a proposed standardized scoring method
• Who was studied: No new patients were studied. The review covered published studies on melanoma, gastrointestinal tract carcinomas, non-small cell lung carcinoma and mesothelioma, endometrial and ovarian carcinomas, squamous cell carcinoma of the head and neck, genitourinary carcinomas, and primary brain tumors.
• Exposure: None studied. The article does not discuss asbestos or any other exposure. Its subject is the lymphocytes found in tumor tissue.
• Main results:
  • The authors reported that earlier studies by other researchers, using immunohistochemistry, suggested TILs were associated with a better prognosis in mesothelioma.
  • The review described unpublished data from a cohort of 329 pleural malignant mesothelioma cases, made up of thoracoscopic pleurodesis biopsies and resection specimens. The data were cited as a personal communication from Russell, Thapa and John.
  • In those 329 pleural malignant mesothelioma cases, the stromal TILs score was reported as strongly negatively correlated with survival. No numerical results were given.
  • In the same cases, the presence of tertiary lymphoid structures was reported as independently associated with better survival in multivariate analysis.
• The authors' conclusion: The authors concluded that their proposed standardized methods should be treated as a tool for further research and as a reference against which other methods can be tested. They hoped the methods would help clinicians, researchers and pathologists evaluate how useful TIL assessment is.
• Limitations the authors state:
  • The authors stated that their proposed consensus methodology has limitations and that many questions remain open.
  • The authors stated that their recommendations may not translate to some tumor types, such as gliomas. For those tumors, a standardized method still needs to be developed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Ovarian cancer.

Medical terms in this study, explained in our Lexicon: Tumor-Infiltrating Lymphocytes, Biomarker, Carcinoma, Mesothelioma, Squamous Cell Carcinoma, Immunotherapy.

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