Assessment of tumor infiltrating lymphocytes (TILs) in histopathological specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible and reliable immuno-oncology biomarkers is clear. In Part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on H&E sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in Part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.

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, gynecological 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.

Stroke is a leading cause of mortality and morbidity in the developed world. The goals of an imaging evaluation for acute stroke are to establish a diagnosis as early as possible and to obtain accurate information about the intracranial vasculature and brain perfusion for guidance in selecting the appropriate therapy. A comprehensive evaluation may be performed with a combination of computed tomography (CT) or magnetic resonance (MR) imaging techniques. Unenhanced CT can be performed quickly, can help identify early signs of stroke, and can help rule out hemorrhage. CT angiography and CT perfusion imaging, respectively, can depict intravascular thrombi and salvageable tissue indicated by a penumbra. These examinations are easy to perform on most helical CT scanners and are increasingly used in stroke imaging protocols to decide whether intervention is necessary. While acute infarcts may be seen early on conventional MR images, diffusion-weighted MR imaging is more sensitive for detection of hyperacute ischemia. Gradient-echo MR sequences can be helpful for detecting a hemorrhage. The status of neck and intracranial vessels can be evaluated with MR angiography, and a mismatch between findings on diffusion and perfusion MR images may be used to predict the presence of a penumbra. The information obtained by combining various imaging techniques may help differentiate patients who do not need intravenous or intraarterial therapy from those who do, and may alter clinical outcomes.