Immunogradient Indicators for Antitumor Response Assessment by Automated Tumor-Stroma Interface Zone Detection

Immuno-Interface Score to Predict Outcome in Colorectal Cancer Independent of Microsatellite Instability Status

“…Our study provides further evidence for the value of the recently proposed Immunogradient indicators as independent prognostic factors reported in CRC and hormone receptor-positive breast cancer patients [ 33 ]. In particular, the CM for CD8+ cell density within the IZ (CD8+ Immunogradient) was a strong independent predictor of better OS in CRC patients (HR: 0.39, p = 0.0071) [ 33 ], similar to that in the current analysis of an independent CRC cohort (HR: 0.31, p = 0.0029, Table 4 ).…”

“…Our study provides further evidence for the value of the recently proposed Immunogradient indicators as independent prognostic factors reported in CRC and hormone receptor-positive breast cancer patients [ 33 ]. In particular, the CM for CD8+ cell density within the IZ (CD8+ Immunogradient) was a strong independent predictor of better OS in CRC patients (HR: 0.39, p = 0.0071) [ 33 ], similar to that in the current analysis of an independent CRC cohort (HR: 0.31, p = 0.0029, Table 4 ). In contrast to other DIA studies, based on enumeration of immune cell densities and their proportions in CT and IM [ 25 ] or distances between the cell populations [ 31 , 32 ] that improved prognostic accuracy, the CM indicator represents directional change (gradient) of immune cell density within the stroma-to-tumor transition TME compartment, automatically sampled as IZ.…”

“…The systematic extraction of the Immunogradient indicators was previously described [ 33 ]. In brief, the WSI of a tumor is processed by DIA software to identify tissue classes for each pixel and to extract coordinates and counts of positive cells.…”

“…an interface zone of width 9 would cover ranks [−4; 4]. For CRC, an IZ of width 3 (ranks [−1; 1]), abbreviated IZ 3 , was previously found optimal [ 33 ]. The tumor aspect (T) (rank = 1) and stroma aspect (S) (rank = −1) of IZ 3 are highlighted in Figure 2 as the red and green hexagons, respectively.…”

“…DIA-based immune profiling analysis was further advanced by Nearchou et al by a combined tumor budding and immune cell quantification and proximity analysis; they proposed a spatial immuno-oncology index based on spatial relationships between tumor buds, TIL and macrophage populations within TME which enabled significant prognostic stratification of stage II CRC [ 31 , 32 ]. Recently, Rasmusson et al proposed a set of Immunogradient indicators which quantifies the immune cell density gradient across the tumor-stroma interface zone (IZ), sampled by an automated hexagonal tiling statistical modeling; the Immunogradient indicators for CD8+ cell density provided independent prognostic value in CRC and hormone receptor positive breast cancer patients [ 33 ].…”