Signals from the tumor microenvironment (TME) have a profound influence on the maintenance and progression of cancers. Chronic inflammation and the infiltration of immune cells in breast cancer (BC) have been strongly associated with early carcinogenic events and a switch to a more immunosuppressive response. Cancer-associated fibroblasts (CAFs) are the most abundant stromal component and can modulate tumor progression according to their secretomes. The immune cells including tumor-infiltrating lymphocytes (TILs) (cytotoxic T cells (CTLs), regulatory T cells (Tregs), and helper T cell (Th)), monocyte-infiltrating cells (MICs), myeloid-derived suppressor cells (MDSCs), mast cells (MCs), and natural killer cells (NKs) play an important part in the immunological balance, fluctuating TME between protumoral and antitumoral responses. In this review article, we have summarized the impact of these immunological players together with CAF secreted substances in driving BC progression. We explain the crosstalk of CAFs and tumor-infiltrating immune cells suppressing antitumor response in BC, proposing these cellular entities as predictive markers of poor prognosis. CAF-tumor-infiltrating immune cell interaction is suggested as an alternative therapeutic strategy to regulate the immunosuppressive microenvironment in BC.

Immunotherapy in the metastatic setting has drastically altered the landscape of treatment for various types of malignancy, including colorectal cancer. The category of immune checkpoint inhibitors has especially emerged as a class of therapy predicated on a more comprehensive understanding of immune cell-cancer cell regulation and evolution of the tumor microenvironment over time. Strategies including adoptive cellular therapies, tumor vaccines, and antibodies have also demonstrated the ability to enhance antitumor immunity. In this article, we provide a comprehensive review of the current landscape of immunotherapeutic strategies in colorectal cancer and provide insight into how these strategies may evolve in the next decade and be adapted to more localized forms of cancers of the colon and rectum. We provide particular focus on various combination approaches under investigation for reversing cancer-induced immunosuppression, especially in mismatch repair-proficient/microsatellite-stable colorectal tumors. Finally, we summarize current understanding on a recently identified integral factor in local immune regulation, the colonic microbiome. The aim of this article is to identify current challenges and barriers to improvement and to specify opportunities for applying knowledge in the immunotherapy sphere to rational design of clinical trials intended to improve survival and related outcomes in patients treated in the neoadjuvant setting.

Autologous hematopoietic stem cell transplantation (ASCT) improves survival for patients with chemotherapy-sensitive lymphoma. Validated scoring systems are used in the clinical setting to predict treatment toxicity and survival; however, complications related to disease and treatment still occur, highlighting challenges in optimal patient selection and the need for novel predictors. Analysis of body composition and muscle mass can provide an objective assessment to identify vulnerable populations, as sarcopenia and frailty have been reported to predict outcomes in other tumor types. In this retrospective cohort study of patients undergoing ASCT for lymphoma, we investigated associations of sarcopenia with clinically significant outcomes, including overall survival (OS) and progression-free survival (PFS). Computed tomography (CT) images of 78 patients obtained routinely pretransplantation were used to assess skeletal muscle mass and are reported as skeletal muscle index (SMI). OS, PFS, and clinical outcomes of interest were compared between groups. Twenty-seven patients (34.6%) in the cohort met the criteria for sarcopenia. Patients with sarcopenia had a significantly shorter 3-year PFS (59% [95% confidence interval (CI), 38% to 75%] versus 84% [95% CI, 71% to 92%]; P = .02) after 3 years of follow up, whereas there was no difference in OS between patients with and those without sarcopenia (78% [95% CI, 57% to 89%] versus 88% [95% CI, 76% to 95%]; P = .25). Interestingly, no difference in survival was found with stratification based on the Karnofsky Performance Scale or Hematopoietic Cell Transplantation-Specific Comorbidity Index. There also were no significant between-group differences in length of hospital stay and the incidences of other clinical outcomes of interest, including febrile neutropenia, mucositis, total parenteral nutrition requirement, acute kidney injury, rate of readmission, or intensive care unit admission. This is the first study to our knowledge to correlate sarcopenia with disease control and PFS after ASCT in lymphoma. Possible explanations include a higher rate of chemotherapy-related toxicity, leading to disruptions of treatment as well as dysfunction of antitumor immunity secondary to impaired regulations from myokines from the loss of muscle mass or an unknown cause that is yet to be elucidated. Physical therapy programs and personalized regimens for treatment based on the analysis of body composition indices can be further studied and implemented to mitigate treatment-related toxicity and to optimize survival in patients with sarcopenia.

Anti-PD-1 based therapies and brentuximab vedotin (BV) have significantly improved survival in patients with classic Hodgkin lymphoma (cHL) and have been incorporated into earlier lines of therapy. However, there is insufficient data regarding the clinical outcomes in patients who develop refractory disease or who become intolerant of BV and anti-PD-1 therapies (double refractory/intolerant; DR/INT). Here, we evaluated outcomes in patients with DR/INT cHL from 15 US academic medical centers. A total of 173 patients were identified as DR/INT. The median overall survival from the time of cHL diagnosis (OS-1) was 14.8 years (95% CI: 10.9–20.9 years) and the 10-year OS-1 estimate was 62% (95% CI: 52–70%). After accounting for differences in age, patients who underwent autologous stem cell transplant prior to developing DR/INT had significantly longer OS-1 (HR 0.53, 95% CI: 0.29–0.96, p = 0.04). Median OS from time of DR/INT (OS-2) was 7.4 years (95% CI: 4.3-NR) and the 5-year OS-2 estimate was 57% (95% CI: 48-66%). Both anti-PD-1 and BV based therapy rechallenge were effective with median PFS of 237 days (95% CI: 155-357 days) and 183 days (95% CI: 108–273 days), respectively. Finally, advanced therapy options such as CD30 directed chimeric antigen receptor T-cell therapy and allogeneic stem cell transplant after DR/INT were associated with improved OS-2 (p < 0.001). To our knowledge, this represents the largest cohort of patients with DR/INT cHL. OS-2 will serve as a benchmark for future studies aiming to improve survival in DR/INT cHL.