SITC Immunotherapy Surrogate Endpoints Initiative

Overview

The Society for Immunotherapy of Cancer (SITC) committed to a number of pathology-centric efforts in 2018 with the formation of the SITC Pathology Taskforce. In 2020, a formal committee was created to organize and lead the integration and consideration of all pathology-related efforts across the Society. Over the last five years, the group has focused their efforts on a series of standardization efforts related to multi-spectral imaging and pathologic response in the neoadjuvant setting.

Publications & Training Modules

The Society for Immunotherapy of Cancer's Pathology Committee has put together a comprehensive pathology initiative aimed at advancing and harmonizing the application of novel pathologic techniques across research and clinical settings. This initiative brings together multidisciplinary expertise to refine methodological standards, promote reproducibility, and support the integration of cutting-edge technologies into routine practice. The scope of these efforts is detailed in the following five manuscripts and related training modules.

SITC PATHdata Study

Immunotherapeutic agents are approved for use in more than a dozen tumor types, with early- and late-stage indications. In the neoadjuvant setting, pathologic response is the endpoint of many clinical trials and can become a surrogate endpoint for overall survival when long-term patient outcomes are available. However, robust datasets to support clinical utility often require meta-analyses of multiple individual studies. The ability to make meaningful comparisons across trials is currently limited by the parallel development and use of different pathologic response scoring criteria and data reporting systems in individual IO clinical trials, both within and across tumor types.

To address these issues, SITC held a PATHdata study to validate the reproducibility of a pan-tumor approach for pathologic response assessment in tissue specimens from patients treated with neoadjuvant IO. This was accomplished using immune-related pathologic response criteria (irPRC) and standardized data reporting. Updated guidelines for neoadjuvant scoring of pathologic response, the results of the multi-institutional study, and subsequent training materials are detailed in the manuscripts linked below.

Multiplex immunohistochemistry (IHC) and immunofluorescence (IF) Best Practices

Understanding how tumors interact with the host immune system has become essential for improving cancer prognosis and treatment strategies. The interaction between the immune system and tumor cells is an important feature for the prognosis and treatment of cancer. Multiplex immunohistochemistry (mIHC) and multiplex immunofluorescence (mIF) analyses are emerging technologies that can be used to help quantify immune cell subsets, their functional state, and their spatial arrangement within the tumor microenvironment. These advanced imaging platforms enable more comprehensive characterization of tumor–immune dynamics than traditional single-plex methods.

As the use of multiplex IHC/IF expands in both research and clinical environments, consistent standards for experimental workflows and data interpretation are urgently needed. To ensure standardization of multiplex IHC/IF adoption in research and clinical settings, the manuscripts below define best practices for multiplex IHC/IF sample handling (staining and validation), image analysis, and data sharing. Together, these companion documents provide a unified framework to support reproducible, high-quality multiplex tissue imaging across laboratories.

SITC MxIF-SIG Initiative

Pathology and specific multiplex imaging, which allows for simultaneous characterization of multiple markers, has been more readily investigated and is envisioned to be critical for the selection of novel therapeutics in the future. Clinical adoption of these technologies, however, remains limited due to various challenges including standardized data reporting methods.

To address this barrier in the field, the SITC Pathology Committee developed the Multiplex Immunofluorescence – Special Interest Group (MxIF-SIG) Initiative, with the primary goal of developing a consensus checklist for multiplex IF and immune histochemistry (IHC) data validation and reporting. The subsequent checklist is detailed in the manuscript linked below.