Cancer remains a significant global health challenge, demanding precise staging for effective prognostic assessments and therapeutic interventions. Despite numerous strategies explored, understanding the intricate interplay between tumors and their microenvironment remains elusive. In this proposal, we propose the investigation of the spatio-temporal dynamics of diverse B7-associated immune cell types, collectively termed as the immunome within infiltrating lung tumors. Variations in B7 molecule densities, such as B7-H3, B7-H4, and B7-H5/Vista, in immune cells or within the core tumor (enriched with PD-L1), have been linked to altered patient survival and recurrence rates. Notably, emerging evidence suggests that the B7-associated immune infiltrate, particularly the myeloid component, holds promise as a pivotal predictive and prognostic factor. However, while various studies have highlighted the heterogeneities within tumoral and infiltrated immune networks in lung carcinoma, the relevance of B7-associated immune control to tumor progression remains inadequately demonstrated. Leveraging this critical gap, we aim to delve deeper into the myeloid and B7 molecule-related contextual landscape to elucidate tumor plasticity and clinical outcomes. Our proposed integrative approach, utilizing multispectral multiplexed fluorescence immunohistochemistry (mFIHC) and high-dimensional digital pathology, seeks to unveil the dynamics of hallmark immune infiltrates and associated microenvironmental changes over time and tumor stages. By discerning the specific cell types that exert a significant impact on clinical outcomes and patient survival, we anticipate that our study will shed light on the contradictory aspects surrounding targets like B7-H3 and Vista. Employing advanced technical methodologies, our endeavor holds the promise of providing novel insights and instilling hope for promising outcomes in cancer therapeutics.